Phospholipid-transporting ATPase IK (also known as ATP8B3 orATP1K) belongs to the subfamily IV of the P-type ATPases family, whose members transport phospholipids across the membrane. The function of ATP8B3 is not clear. Unlike other type IV members (ATP8B1,2,4), ATP8B3 does not seem to interact with either CDC50A or CDC50B []. It is exclusively expressed in the testis where it localises to the acrosomes of spermatids, the organelle which develops in the anterior half of the head of spermatozoa []. However, the disruption of ATP8B3 in mice does not affect sperm morphology or fertilisation rate [].
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers []. In eukaryotic cells, K+channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].All K+channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+channels; and three types of calcium (Ca)-activated K+channels (BK, IK and SK) []. The 2TM domain family comprises inward-rectifying K+channels. In addition, there are K+channel alpha-subunits that possess two P-domains. These are usually highly regulated K+selective leak channels.This entry represents the the voltage-gated Kv channel and the KCNQ channel. KCNQ channels differ from other voltage-gated 6 TM helix channels, chiefly in that they possess no tetramerisation domain.
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers []. In eukaryotic cells, K+channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].All K+channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+channels; and three types of calcium (Ca)-activated K+channels (BK, IK and SK) []. The 2TM domain family comprises inward-rectifying K+channels. In addition, there are K+channel alpha-subunits that possess two P-domains. These are usually highly regulated K+selective leak channels.The Kv family can be divided into several subfamilies on the basis of sequence similarity and function. Four of these subfamilies, Kv1 (Shaker), Kv2 (Shab), Kv3 (Shaw) and Kv4 (Shal), consist of pore-forming alpha subunits that associate with different types of beta subunit. Each alpha subunit comprises six hydrophobic TM domains with a P-domain between the fifth and sixth, which partially resides in the membrane. The fourth TM domain has positively charged residues at every third residue and acts as a voltage sensor, which triggers the conformational change that opens the channel pore in response to a displacement in membrane potential []. More recently, 4 new electrically-silent alpha subunits have been cloned: Kv5 (KCNF), Kv6 (KCNG), Kv8 and Kv9 (KCNS). These subunits do not themselves possess any functional activity, but appear to form heteromeric channels with Kv2 subunits, and thus modulate Shab channel activity []. When highly expressed, they inhibit channel activity, but at lower levels show more specific modulatory actions.The Shal potassium channel was found in Drosophila melanogaster (Fruit fly). Several vertebrate potassium channels with similar amino acid sequences were subsequently found and, together with the D. melanogaster Shal channel, now constitute the Kv4 family. These channels are the primary subunits contributing to transient, voltage-dependent potassium currents in the nervous system (A currents) and the heart (transient outward current), and are inhibited by free fatty acids []. This family can be further divided into 3 subfamilies, designated Kv4.1(KCND1), Kv4.2(KCND2) and Kv4.3(KCND3).
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers []. In eukaryotic cells, K+channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].All K+channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+channels; and three types of calcium (Ca)-activated K+channels (BK, IK and SK) []. The 2TM domain family comprises inward-rectifying K+channels. In addition, there are K+channel alpha-subunits that possess two P-domains. These are usually highly regulated K+selective leak channels.The Kv family can be divided into several subfamilies on the basis of sequence similarity and function. Four of these subfamilies, Kv1 (Shaker), Kv2 (Shab), Kv3 (Shaw) and Kv4 (Shal), consist of pore-forming alpha subunits that associate with different types of beta subunit. Each alpha subunit comprises six hydrophobic TM domains with a P-domain between the fifth and sixth, which partially resides in the membrane. The fourth TM domain has positively charged residues at every third residue and acts as a voltage sensor, which triggers the conformational change that opens the channel pore in response to a displacement in membrane potential []. More recently, 4 new electrically-silent alpha subunits have been cloned: Kv5 (KCNF), Kv6 (KCNG), Kv8 and Kv9 (KCNS). These subunits do not themselves possess any functional activity, but appear to form heteromeric channels with Kv2 subunits, and thus modulate Shab channel activity []. When highly expressed, they inhibit channel activity, but at lower levels show more specific modulatory actions.The Kv2 voltage-dependent potassium channels (also known as the Shab family) are responsible for much of the delayed rectifier current in Drosophila melanogaster (Fruit fly) nervous system and muscle. However, in vertebrates, Kv2 channels have been shwon to be involved in the delayed rectifier currents of the heart and skeletal muscles. They are also thought to be important in determining intrinsic neuronal excitability in both mammals and non-mammals []. Kv2 channels can be further divided into 2 subtypes, designated Kv2.1 and Kv2.2.This entry represents the voltage-dependent Kv2 potassium channels.
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers []. In eukaryotic cells, K+channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].All K+channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+channels; and three types of calcium (Ca)-activated K+channels (BK, IK and SK) []. The 2TM domain family comprises inward-rectifying K+channels. In addition, there are K+channel alpha-subunits that possess two P-domains. These are usually highly regulated K+selective leak channels.Inwardly-rectifying potassium channels (Kir) are the principal class of two-TM domain potassium channels. They are characterised by the property of inward-rectification, which is described as the ability to allow large inward currents and smaller outward currents. Inwardly rectifying potassium channels (Kir) are responsible for regulating diverse processes including: cellular excitability, vascular tone, heart rate, renal salt flow, and insulin release []. To date, around twenty members of this superfamily have been cloned, which can be grouped into six families by sequence similarity, and these are designated Kir1.x-6.x [, ].Cloned Kir channel cDNAs encode proteins of between ~370-500 residues, both N- and C-termini are thought to be cytoplasmic, and the N terminus lacks a signal sequence. Kir channel alpha subunits possess only 2TM domains linked with a P-domain. Thus, Kir channels share similarity with the fifth and sixth domains, and P-domain of the other families. It is thought that four Kir subunits assemble to form a tetrameric channel complex, which may be hetero- or homomeric [].
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers []. In eukaryotic cells, K+channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].All K+channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+channels; and three types of calcium (Ca)-activated K+channels (BK, IK and SK) []. The 2TM domain family comprises inward-rectifying K+channels. In addition, there are K+channel alpha-subunits that possess two P-domains. These are usually highly regulated K+selective leak channels.Inwardly-rectifying potassium channels (Kir) are the principal class of two-TM domain potassium channels. They are characterised by the property of inward-rectification, which is described as the ability to allow large inward currents and smaller outward currents. Inwardly rectifying potassium channels (Kir) are responsible for regulating diverse processes including: cellular excitability, vascular tone, heart rate, renal salt flow, and insulin release []. To date, around twenty members of this superfamily have been cloned, which can be grouped into six families by sequence similarity, and these are designated Kir1.x-6.x [, ].Cloned Kir channel cDNAs encode proteins of between ~370-500 residues, both N- and C-termini are thought to be cytoplasmic, and the N terminus lacks a signal sequence. Kir channel alpha subunits possess only 2TM domains linked with a P-domain. Thus, Kir channels share similarity with the fifth and sixth domains, and P-domain of the other families. It is thought that four Kir subunits assemble to form a tetrameric channel complex, which may be hetero- or homomeric [].Kir1.1 channels (also known as ROMK1-6 and KAB-1) are thought to underlieK+secretion in the kidney. Their activity is modulated by intracellular pH, with acidosis inhibiting the channel. Both N- and C-termini are thought to be involved in this modulation. Mutations in Kir1.1 lead to Bartter's syndrome type III, an inherited kidney disorder, which leads to salt-wasting, hypokalaemia and metabolic acidosis. All of the mutations thathave been functionally characterised either abolish, or markedly reduce,Kir1.1 K+currents.
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers []. In eukaryotic cells, K+channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].All K+channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdividedinto conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+channels; and three types of calcium (Ca)-activated K+channels (BK, IK and SK) []. The 2TM domain family comprises inward-rectifying K+channels. In addition, there are K+channel alpha-subunits that possess two P-domains. These are usually highly regulated K+selective leak channels.Inwardly-rectifying potassium channels (Kir) are the principal class of two-TM domain potassium channels. They are characterised by the property of inward-rectification, which is described as the ability to allow large inward currents and smaller outward currents. Inwardly rectifying potassium channels (Kir) are responsible for regulating diverse processes including: cellular excitability, vascular tone, heart rate, renal salt flow, and insulin release []. To date, around twenty members of this superfamily have been cloned, which can be grouped into six families by sequence similarity, and these are designated Kir1.x-6.x [, ].Cloned Kir channel cDNAs encode proteins of between ~370-500 residues, both N- and C-termini are thought to be cytoplasmic, and the N terminus lacks a signal sequence. Kir channel alpha subunits possess only 2TM domains linked with a P-domain. Thus, Kir channels share similarity with the fifth and sixth domains, and P-domain of the other families. It is thought that four Kir subunits assemble to form a tetrameric channel complex, which may be hetero- or homomeric [].The Kir1.2 channel (also known as Kir4.1, ROMK2, BIR10, KAB-2 and BIRK1) is found principally inthe brain, where it is widely distributed. It has also been found on satellite cells of the rat cochlear ganglia, and at low levels within the kidney. Kir1.2 channel activity is dependent upon phosphorylation-state, with two serine residues within the C terminus, likely the target of PKA protein kinase A, being involved []. Kir1.2 has recently been shown to interact with a novel PDZ domain-containing protein, CIPP [].
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers []. In eukaryotic cells, K+channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].All K+channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+channels; and three types of calcium (Ca)-activated K+channels (BK, IK and SK) []. The 2TM domain family comprises inward-rectifying K+channels. In addition, there are K+channel alpha-subunits that possess two P-domains. These are usually highly regulated K+selective leak channels.Inwardly-rectifying potassium channels (Kir) are the principal class of two-TM domain potassium channels. They are characterised by the property of inward-rectification, which is described as the ability to allow large inward currents and smaller outward currents. Inwardly rectifying potassium channels (Kir) are responsible for regulating diverse processes including: cellular excitability, vascular tone, heart rate, renal salt flow, and insulin release []. To date, around twenty members of this superfamily have been cloned, which can be grouped into six families by sequence similarity, and these are designated Kir1.x-6.x [, ].Cloned Kir channel cDNAs encode proteins of between ~370-500 residues, both N- and C-termini are thought to be cytoplasmic, and the N terminus lacks a signal sequence. Kir channel alpha subunits possess only 2TM domains linked with a P-domain. Thus, Kir channels share similarity with the fifth and sixth domains, and P-domain of the other families. It is thought that four Kir subunits assemble to form a tetrameric channel complex, which may be hetero- or homomeric [].Kir2.1 (also known as IRK1) is thought to play a role in controlling theexcitability of brain and heart tissues. Immuno-localisation studies haverevealed it to be present on many cell types within the forebrain, includingneurones, macroglia, endothelial, ependymal and vascular smooth musclecells. Phosphatidylinositol 4,5-bisphosphate (PIP2) is thought to interactwith Kir2.1 (as well as several other Kir subunits) via a C-terminal motif,promoting channel activity. Recently it has been demonstrated that nicotinecan block Kir2.1 channels, this likely contributing to its ability topromote the occurrence of cardiac arrhythmias [].
Inwardly-rectifying potassium channels (Kir) are the principal class of two-TM domain potassium channels. They are characterised by the property of inward-rectification, which is described as the ability to allow large inward currents and smaller outward currents. Inwardly rectifying potassium channels (Kir) are responsible for regulating diverse processes including: cellular excitability, vascular tone, heart rate, renal salt flow, and insulin release []. To date, around twenty members of this superfamily have been cloned, which can be grouped into six families by sequence similarity, and these are designated Kir1.x-6.x [, ].Cloned Kir channel cDNAs encode proteins of between ~370-500 residues, both N- and C-termini are thought to be cytoplasmic, and the N terminus lacks a signal sequence. Kir channel alpha subunits possess only 2TM domains linked with a P-domain. Thus, Kir channels share similarity with the fifth and sixth domains, and P-domain of the other families. It is thought that four Kir subunits assemble to form a tetrameric channel complex, which may be hetero- or homomeric [].Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers []. In eukaryotic cells, K+channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].All K+channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+channels; and three types of calcium (Ca)-activated K+channels (BK, IK and SK) []. The 2TM domain family comprises inward-rectifying K+channels. In addition, there are K+channel alpha-subunits that possess two P-domains. These are usually highly regulated K+selective leak channels.Kir5 channels are significantly expressed in kidney, pancreas and thyroidgland, suggesting that they may be involved in the regulation of fluid andpH balance.
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers []. In eukaryotic cells, K+channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].All K+channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+channels; and three types of calcium (Ca)-activated K+channels (BK, IK and SK) []. The 2TM domain family comprises inward-rectifying K+channels. In addition, there are K+channel alpha-subunits that possess two P-domains. These are usually highly regulated K+selective leak channels.Inwardly-rectifying potassium channels (Kir) are the principal class of two-TM domain potassium channels. They are characterised by the property of inward-rectification, which is described as the ability to allow large inward currents and smaller outward currents. Inwardly rectifying potassium channels (Kir) are responsible for regulating diverse processes including: cellular excitability, vascular tone, heart rate, renal salt flow, and insulin release []. To date, around twenty members of this superfamily have been cloned, which can be grouped into six families by sequence similarity, and these are designated Kir1.x-6.x [, ].Cloned Kir channel cDNAs encode proteins of between ~370-500 residues, both N- and C-termini are thought to be cytoplasmic, and the N terminus lacks a signal sequence. Kir channel alpha subunits possess only 2TM domains linked with a P-domain. Thus, Kir channels share similarity with the fifth and sixth domains, and P-domain of the other families. It is thought that four Kir subunits assemble to form a tetrameric channel complex, which may be hetero- or homomeric [].Kir2.2 (also known as IRK2/BIR8), like other Kir2.x family members, hasbeen found to be expressed in the brain. Immuno-localisation studies haverevealed it is primarily expressed in the cerebellum, as opposed to theforebrain (cf. Kir1.1). It is also expressed to lower extents in thekidney, heart and skeletal muscle. When heterologously expressed in Xenopusoocytes, human Kir2.2 produced strong, inwardly rectifying K+currents.Co-expression of Kir2.2v (a closely related Kir2.x subunit) with Kir2.2caused an inhibition of induced K+currents, indicating that it likelyfunctions as a negative regulator of Kir2.2 [].This family also includes Kir2.6, which is nearly identical to Kir2.2 [].
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers []. In eukaryotic cells, K+channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].All K+channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+channels; and three types of calcium (Ca)-activated K+channels (BK, IK and SK) []. The 2TM domain family comprises inward-rectifying K+channels. In addition, there are K+channel alpha-subunits that possess two P-domains. These are usually highly regulated K+selective leak channels.Inwardly-rectifying potassium channels (Kir) are the principal class of two-TM domain potassium channels. They are characterised by the property of inward-rectification, which is described as the ability to allow large inward currents and smaller outward currents. Inwardly rectifying potassium channels (Kir) are responsible for regulating diverse processes including: cellular excitability, vascular tone, heart rate, renal salt flow, and insulin release []. To date, around twenty members of this superfamily have been cloned, which can be grouped into six families by sequence similarity, and these are designated Kir1.x-6.x [, ].Cloned Kir channel cDNAs encode proteins of between ~370-500 residues, both N- and C-termini are thought to be cytoplasmic, and the N terminus lacks a signal sequence. Kir channel alpha subunits possess only 2TM domains linked with a P-domain. Thus, Kir channels share similarity with the fifth and sixth domains, and P-domain of the other families. It is thought that four Kir subunits assemble to form a tetrameric channel complex, which may be hetero- or homomeric [].Kir2.3 it thought to play a role in the maintenance of membrane potentialin both neurones and myocardium. It is highly expressed in the forebrain,and has a distinctly smaller ionic conductance than other Kir2.x familymembers. By comparison with other Kir2.x channels, sequence analysis showsit to have a larger putative extracellular loop (~15 more amino acidresidues) linking the first TM domain to the pore-forming (H5) domain, although the significance of this remains to be elucidated. Functionalstudies have revealed Kir2.3 channel activity to be modulated by channelphosphorylation, oxidation state, and changes in intracellular andextracellular pH.
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers []. In eukaryotic cells, K+channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].All K+channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+channels; and three types of calcium (Ca)-activated K+channels (BK, IK and SK) []. The 2TM domain family comprises inward-rectifying K+channels. In addition, there are K+channel alpha-subunits that possess two P-domains. These are usually highly regulated K+selective leak channels.Inwardly-rectifying potassium channels (Kir) are the principal class of two-TM domain potassium channels. They are characterised by the property of inward-rectification, which is described as the ability to allow large inward currents and smaller outward currents. Inwardly rectifying potassium channels (Kir) are responsible for regulating diverse processes including: cellular excitability, vascular tone, heart rate, renal salt flow, and insulin release []. To date, around twenty members of this superfamily have been cloned, which can be grouped into six families by sequence similarity, and these are designated Kir1.x-6.x [, ].Cloned Kir channel cDNAs encode proteins of between ~370-500 residues, both N- and C-termini are thought to be cytoplasmic, and the N terminus lacks a signal sequence. Kir channel alpha subunits possess only 2TM domains linked with a P-domain. Thus, Kir channels share similarity with the fifth and sixth domains, and P-domain of the other families. It is thought that four Kir subunits assemble to form a tetrameric channel complex, which may be hetero- or homomeric [].The Kir3.x channel family is gated by G-proteins following G-proteincoupled receptor (GPCR) activation. They are widely distributed inneuronal, atrial, and endocrine tissues and play key roles in generatinglate inhibitory postsynaptic potentials, slowing the heart rate andmodulating hormone release. They are directly activated by G-proteinbeta-gamma subunits released from G-protein heterotrimers of the G(i/o)family upon appropriate receptor stimulation.Kir3.1 channels are thought to form heteromers in vivo: in heart,consisting of Kir3.1 and Kir3.2, and in brain, Kir3.1 with Kir 3.4.
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers []. In eukaryotic cells, K+channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].All K+channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+channels; and three types of calcium (Ca)-activated K+channels (BK, IK and SK) []. The 2TM domain family comprises inward-rectifying K+channels. In addition, there are K+channel alpha-subunits that possess two P-domains. These are usually highly regulated K+selective leak channels.Inwardly-rectifying potassium channels (Kir) are the principal class of two-TM domain potassium channels. They are characterised by the property of inward-rectification, which is described as the ability to allow large inward currents and smaller outward currents. Inwardly rectifying potassium channels (Kir) are responsible for regulating diverse processes including: cellular excitability, vascular tone, heart rate, renal salt flow, and insulin release []. To date, around twenty members of this superfamily have been cloned, which can be grouped into six families by sequence similarity, and these are designated Kir1.x-6.x [, ].Cloned Kir channel cDNAs encode proteins of between ~370-500 residues, both N- and C-termini are thought to be cytoplasmic, and the N terminus lacks a signal sequence. Kir channel alpha subunits possess only 2TM domains linked with a P-domain. Thus, Kir channels share similarity with the fifth and sixth domains, and P-domain of the other families. It is thought that four Kir subunits assemble to form a tetrameric channel complex, which may be hetero- or homomeric [].The Kir3.x channel family is gated by G-proteins following G-proteincoupled receptor (GPCR) activation. They are widely distributed inneuronal, atrial, and endocrine tissues and play key roles in generatinglate inhibitory postsynaptic potentials, slowing the heart rate andmodulating hormone release. They are directly activated by G-proteinbeta-gamma subunits released from G-protein heterotrimers of the G(i/o)family upon appropriate receptor stimulation.Kir3.3 does not generate receptor-evoked, or constitutively-active K+currents, when heterologously expressed in Xenopus oocytes. It maytherefore contribute to Kir channel diversity by associating with otherKir3.x family members [].
Two types of beta subunit (KCNE and KCNAB) are presently known to associate with voltage-gated alpha subunits (Kv, KCNQ and eag-like). However, not all combinations of alpha and beta subunits are possible. The KCNE family of K+ channel subunits are membrane glycoproteins that possess a single transmembrane (TM) domain. They share no structural relationship with the alpha subunit proteins, which possess pore forming domains. The subunits appear to have a regulatory function, modulating the kinetics and voltage dependence of the alpha subunits of voltage-dependent K+ channels. KCNE subunits are formed from short polypeptides of ~130 amino acids, and are divided into five subfamilies: KCNE1 (MinK/IsK), KCNE2 (MiRP1), KCNE3 (MiRP2), KCNE4 (MiRP3) and KCNE1L (AMMECR2). Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers []. In eukaryotic cells, K+channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].All K+channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+channels; and three types of calcium (Ca)-activated K+channels (BK, IK and SK) []. The 2TM domain family comprises inward-rectifying K+channels. In addition, there are K+channel alpha-subunits that possess two P-domains. These are usually highly regulated K+selective leak channels.
KCNE1 (Potassium voltage-gated channel subfamily E member 1, also known as Mink) subunits associate with KCNQ1 alpha subunits to form channels that are responsible for the IkS currents that determine the duration of the action potential in cardiac muscle []. Mutations in both of the genes encoding these subunits cause an inherited disorder that increases the risk of death from cardiac arrhythmia (long QT syndrome type 1) and Jervell and Lange-Nielsen syndrome, associated with congenital deafness [].Two types of beta subunit (KCNE and KCNAB) are presently known to associate with voltage-gated alpha subunits (Kv, KCNQ and eag-like). However, not all combinations of alpha and beta subunits are possible. The KCNE family of K+ channel subunits are membrane glycoproteins that possess a single transmembrane (TM) domain. They share no structural relationship with the alpha subunit proteins, which possess pore forming domains. The subunits appear to have a regulatory function, modulating the kinetics and voltage dependence of the alpha subunits of voltage-dependent K+ channels. KCNE subunits are formed from short polypeptides of ~130 amino acids, and are divided into five subfamilies: KCNE1 (MinK/IsK), KCNE2 (MiRP1), KCNE3 (MiRP2), KCNE4 (MiRP3) and KCNE1L (AMMECR2). Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers []. In eukaryotic cells, K+channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].All K+channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+channels; and three types of calcium (Ca)-activated K+channels (BK, IK and SK) []. The 2TM domain family comprises inward-rectifying K+channels. In addition, there are K+channel alpha-subunits that possess two P-domains. These are usually highly regulated K+selective leak channels.
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers []. In eukaryotic cells, K+channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].All K+channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+channels; and three types of calcium (Ca)-activated K+channels (BK, IK and SK) []. The 2TM domain family comprises inward-rectifying K+channels. In addition, there are K+channel alpha-subunits that possess two P-domains. These are usually highly regulated K+selective leak channels.Two types of beta subunit (KCNE and KCNAB) are presently known to associate with voltage-gated alpha subunits (Kv, KCNQ and eag-like). However, not all combinations of alpha and beta subunits are possible. The KCNE family of K+ channel subunits are membrane glycoproteins that possess a single transmembrane (TM) domain. They share no structural relationship with the alpha subunit proteins, which possess pore forming domains. The subunits appear to have a regulatory function, modulating the kinetics and voltage dependence of the alpha subunits of voltage-dependent K+ channels. KCNE subunits are formed from short polypeptides of ~130 amino acids, and are divided into five subfamilies: KCNE1 (MinK/IsK), KCNE2 (MiRP1), KCNE3 (MiRP2), KCNE4 (MiRP3) and KCNE1L (AMMECR2). KCNE2 subunits associate with the eag-like HERG alpha subunits, which arethe pore-forming subunits of cardiac IKr channels. Channels formed solelyfrom HERG subunits display similar properties to native IKr channels;however, they differ in their gating and single channel conductance. Channels formed from both KCNE2 and HERG exhibit properties that are identical to those seen in native IKr channels. Three mutations in the KCNE2gene are associated with long QT syndrome and ventricular fibrillation. These mutations result in channels that open slower and close more rapidly,the net effect being a reduced K+ current [].
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers []. In eukaryotic cells, K+channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].All K+channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+channels; and three types of calcium (Ca)-activated K+channels (BK, IK and SK) []. The 2TM domain family comprises inward-rectifying K+channels. In addition, there are K+channel alpha-subunits that possess two P-domains. These are usually highly regulated K+selective leak channels.Two types of beta subunit (KCNE and KCNAB) are presently known to associate with voltage-gated alpha subunits (Kv, KCNQ and eag-like). However, not all combinations of alpha and beta subunits are possible. The KCNE family of K+ channel subunits are membrane glycoproteins that possess a single transmembrane (TM) domain. They share no structural relationship with the alpha subunit proteins, which possess pore forming domains. The subunits appear to have a regulatory function, modulating the kinetics and voltage dependence of the alpha subunits of voltage-dependent K+ channels. KCNE subunits are formed from short polypeptides of ~130 amino acids, and are divided into five subfamilies: KCNE1 (MinK/IsK), KCNE2 (MiRP1), KCNE3 (MiRP2), KCNE4 (MiRP3) and KCNE1L (AMMECR2). KCNE3 is known to associate with the pore forming subunits KCNQ1, KCNQ4,HERG and Kv3.4. KCNE3 forms complexes with Kv3.4 in skeletal muscle -KCNE3 mutations have been identified in families with skeletal muscledisorders []. In the intestine, KCNE3 associates with KCNQ1 to formchannels that are stimulated by cAMP and are thought to be involved insecretory diarrhoea and cystic fibrosis [].
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers []. In eukaryotic cells, K+channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].All K+channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+channels; and three types of calcium (Ca)-activated K+channels (BK, IK and SK) []. The 2TM domain family comprises inward-rectifying K+channels. In addition, there are K+channel alpha-subunits that possess two P-domains. These are usually highly regulated K+selective leak channels.The Kv family can be divided into several subfamilies on the basis of sequence similarity and function. Four of these subfamilies, Kv1 (Shaker), Kv2 (Shab), Kv3 (Shaw) and Kv4 (Shal), consist of pore-forming alpha subunits that associate with different types of beta subunit. Each alpha subunit comprises six hydrophobic TM domains with a P-domain between the fifth and sixth, which partially resides in the membrane. The fourth TM domain has positively charged residues at every third residue and acts as a voltage sensor, which triggers the conformational change that opens the channel pore in response to a displacement in membrane potential []. More recently, 4 new electrically-silent alpha subunits have been cloned: Kv5 (KCNF), Kv6 (KCNG), Kv8 and Kv9 (KCNS). These subunits do not themselves possess any functional activity, but appear to form heteromeric channels with Kv2 subunits, and thus modulate Shab channel activity []. When highly expressed, they inhibit channel activity, but at lower levels show more specific modulatory actions.The Shal potassium channel was found in Drosophila melanogaster (Fruit fly). Several vertebrate potassium channels with similar amino acid sequences were subsequently found and, together with the D. melanogaster Shal channel, now constitute the Kv4 family. These channels are the primary subunits contributing to transient, voltage-dependent potassium currents in the nervous system (A currents) and the heart (transient outward current), and are inhibited by free fatty acids []. This family can be further divided into 3 subfamilies, designated Kv4.1(KCND1), Kv4.2(KCND2) and Kv4.3(KCND3).This uncharacterised C-terminal domain is associated with the Shal (Kv4) potassium channel.
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' group and therapidly inactivating 'transient' group.These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers []. In eukaryotic cells, K+channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].All K+channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+channels; and three types of calcium (Ca)-activated K+channels (BK, IK and SK) []. The 2TM domain family comprises inward-rectifying K+channels. In addition, there are K+channel alpha-subunits that possess two P-domains. These are usually highly regulated K+selective leak channels.The first EAG K+ channel was identified in Drosophila melanogaster (Fruit fly), following a screen for mutations giving rise to behavioural abnormalities. Disruption of the Eag gene caused an ether-induced, leg-shaking behaviour. Subsequent studies have revealed a conserved multi-gene family of EAG-like K+ channels, which are present in human and many other species. Based on the varying functional properties of the channels, the family has been divided into 3 subfamilies: EAG, ELK and ERG. Interestingly, Caenorhabditis elegans appears to lack the ELK type [].The human ether-a-go-go-related gene (HERG), cloned from hippocampus, shares 49% amino acid identity with EAG. It is also found in the heart, where it helps to control K+ efflux []. Mutations in HERG result in the disruption of the repolarising current and the disease LQT2 syndrome, an inheriteddisorder of cardiac repolarisation that predisposes affected individuals tolife-threatening arrhythmias [].
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers []. In eukaryotic cells, K+channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].All K+channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+channels; and three types of calcium (Ca)-activated K+channels (BK, IK and SK) []. The 2TM domain family comprises inward-rectifying K+channels. In addition, there are K+channel alpha-subunits that possess two P-domains. These are usually highly regulated K+selective leak channels.The first EAG K+ channel was identified in Drosophila melanogaster (Fruit fly), following a screen for mutations giving rise to behavioural abnormalities. Disruption of the Eag gene caused an ether-induced, leg-shaking behaviour. Subsequent studies have revealed a conserved multi-gene family of EAG-like K+ channels, which are present in human and many other species. Based on the varying functional properties of the channels, the family has been divided into 3 subfamilies: EAG, ELK and ERG. Interestingly, Caenorhabditis elegans appears to lack the ELK type [].The EAG subfamily has been expressed in heterologous systems to reveal their biophysical and pharmacological functions and to determine their currents in native tissues. All mammalian EAG subfamily K+ channels that have been identified have properties typical of delayed rectifiers, with no measurable inactivation []. Only the Drosophila melanogaster Eag channel exhibits partial inactivation.
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers []. In eukaryotic cells, K+channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].All K+channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+channels; and three types of calcium (Ca)-activated K+channels (BK, IK and SK) []. The 2TM domain family comprises inward-rectifying K+channels. In addition, there are K+channel alpha-subunits that possess two P-domains. These are usually highly regulated K+selective leak channels.The first EAG K+ channel was identified in Drosophila melanogaster (Fruit fly), following a screen for mutations giving rise to behavioural abnormalities. Disruption of the Eag gene caused an ether-induced, leg-shaking behaviour. Subsequent studies have revealed a conserved multi-gene family of EAG-like K+ channels, which are present in human and many other species. Based on the varying functional properties of the channels, the family has been divided into 3 subfamilies: EAG, ELK and ERG. Interestingly, Caenorhabditis elegans appears to lack the ELK type [].
This entry consists of the voltage-dependent potassium channel beta subunit KCNAB and related proteins. The bacterial proteins in this entry lack apparent alpha subunit partners and predicted to function as soluble aldo/keto reductase enzymes [, ].Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers []. In eukaryotic cells, K+channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].All K+channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+channels; and three types of calcium (Ca)-activated K+channels (BK, IK and SK) []. The 2TM domain family comprises inward-rectifying K+channels. In addition, there are K+channel alpha-subunits that possess two P-domains. These are usually highly regulated K+selective leak channels.The KCNAB family (also known as the Kvbeta family) of voltage-dependent potassium channel beta subunits form complexes with the alpha subunits which can modify the properties of the channel. Four of these soluble beta subunits form a complex with four alpha subunit cytoplasmic (T1) regions. These subunits belong to the family of are NADPH-dependent aldo-keto reductases, and bind NADPH-cofactors in their active sites. Changes in the oxidoreductase activity appear to markedly influence the gating mode of Kv channels, since mutations to the catalytic residues in the active site lessen the inactivating activity of KCNAB []. The KCNAB family is further divided into 3 subfamilies: KCNAB1 (Kvbeta1), KCNAB2 (Kvbeta2) and KCNAB3 (Kvbeta3).
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers []. In eukaryotic cells, K+channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].All K+channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+channels; and three types of calcium (Ca)-activated K+channels (BK, IK and SK) []. The 2TM domain family comprises inward-rectifying K+channels. In addition, there are K+channel alpha-subunits that possess two P-domains. These are usually highly regulated K+selective leak channels.The KCNAB family (also known as the Kvbeta family) of voltage-dependent potassium channel beta subunits form complexes with the alpha subunits which can modify the properties of the channel. Four of these soluble beta subunits form a complex with four alpha subunit cytoplasmic (T1) regions. These subunits belong to the family of are NADPH-dependent aldo-keto reductases, and bind NADPH-cofactors in their active sites. Changes in the oxidoreductase activity appear to markedly influence the gating mode of Kv channels, since mutations to the catalytic residues in the active site lessen the inactivating activity of KCNAB []. The KCNAB family is further divided into 3 subfamilies: KCNAB1 (Kvbeta1), KCNAB2 (Kvbeta2) and KCNAB3 (Kvbeta3).
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers []. In eukaryotic cells, K+channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].All K+channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+channels; and three types of calcium (Ca)-activated K+channels (BK, IK and SK) []. The 2TM domain family comprises inward-rectifying K+channels. In addition, there are K+channel alpha-subunits that possess two P-domains. These are usually highly regulated K+selective leak channels.The THIK (Tandem pore-domain Halothane Inhibited K+ channel) family contains two members: THIK-1 and THIK-2. Both proteins were first isolated from rat and have subsequently been found in human. THIK-1 is expressed ubiquitously and is activated by arachidonic acid and inhibited by the volatile anaesthetic halothane. The second member, THIK-2, shares 58% amino acid identity with THIK-1, but is not functionally expressed. THIK-2 is strongly expressed in several tissues, and is particularly abundant in the brain [].
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers []. In eukaryotic cells, K+channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].All K+channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+channels; and three types of calcium (Ca)-activated K+channels (BK, IK and SK) []. The 2TM domain family comprises inward-rectifying K+channels. In addition, there are K+channel alpha-subunits that possess two P-domains. These are usually highly regulated K+selective leak channels.2P-domain channels influence the resting membrane potential and as a result can control cell excitability. In addition, they pass K+in response to changes in membrane potential, and are also tightly regulated by molecular oxygen, GABA (gamma-aminobutyric acid), noradrenaline and serotonin.The first member of this family (TOK1), cloned from Saccharomyces cerevisiae [], ispredicted to have eight potential transmembrane (TM) helices. However,subsequently-cloned two P-domain family members from Drosophila andmammalian species are predicted to have only four TM segments. They areusually referred to as TWIK-related channels (Tandem of P-domains in a Weakly Inward rectifying K+ channel) [, , , ]. Functional characterisation of these channels has revealed a diversity of properties in that they may show inward or outward rectification, their activity may be modulated in different directions by protein phosphorylation, and their sensitivity to changes in intracellular or extracellular pH varies. Despite these disparate properties, they are all thought to share the same topology offour TM segments, including two P-domains. That TWIK-related K+ channelsall produce instantaneous and non-inactivating K+ currents, which do notdisplay a voltage-dependent activation threshold, suggests that they arebackground (leak) K+ channels involved in the generation and modulation of the resting membrane potential in various cell types. Further studies have revealed that they may be found in many species, including: plants, invertebrates and mammals.
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers []. In eukaryotic cells, K+channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].All K+channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+channels; and three types of calcium (Ca)-activated K+channels (BK, IK and SK) []. The 2TM domain family comprises inward-rectifying K+channels. In addition, there are K+channel alpha-subunits that possess two P-domains. These are usually highly regulated K+selective leak channels.The Kv family can be divided into several subfamilies on the basis of sequence similarity and function. Four of these subfamilies, Kv1 (Shaker), Kv2 (Shab), Kv3 (Shaw) and Kv4 (Shal), consist of pore-forming alpha subunits that associate with different types of beta subunit. Each alpha subunit comprises six hydrophobic TM domains with a P-domain between the fifth and sixth, which partially resides in the membrane. The fourth TM domain has positively charged residues at every third residue and acts as a voltage sensor, which triggers the conformational change that opens the channel pore in response to a displacement in membrane potential []. More recently, 4 new electrically-silent alpha subunits have been cloned: Kv5 (KCNF), Kv6 (KCNG), Kv8 and Kv9 (KCNS). These subunits do not themselves possess any functional activity, but appear to form heteromeric channels with Kv2 subunits, and thus modulate Shab channel activity []. When highly expressed, they inhibit channel activity, but at lower levels show more specific modulatory actions.A voltage-dependent potassium channel gene designated Shaw was initially isolated from Drosophila melanogaster (Fruit fly). Subsequently, several vetebrate potassium channels with similar amino acid sequences were found and, together with the D. melanogaster channel, now constitute the Kv3 family. These channels are thought to play a role in shortening of action potential durations and modulating pre-synaptic neurotransmitter release. In mammals, the family consists of 4 genes (Kv3.1, Kv3.2, Kv3.3 and Kv3.4). Each gene product has its own subcellular location and function.
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers []. In eukaryotic cells, K+channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].All K+channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. Thefunctional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+channels; and three types of calcium (Ca)-activated K+channels (BK, IK and SK) []. The 2TM domain family comprises inward-rectifying K+channels. In addition, there are K+channel alpha-subunits that possess two P-domains. These are usually highly regulated K+selective leak channels.The KCNAB family (also known as the Kvbeta family) of voltage-dependent potassium channel beta subunits form complexes with the alpha subunits which can modify the properties of the channel. Four of these soluble beta subunits form a complex with four alpha subunit cytoplasmic (T1) regions. These subunits belong to the family of are NADPH-dependent aldo-keto reductases, and bind NADPH-cofactors in their active sites. Changes in the oxidoreductase activity appear to markedly influence the gating mode of Kv channels, since mutations to the catalytic residues in the active site lessen the inactivating activity of KCNAB []. The KCNAB family is further divided into 3 subfamilies: KCNAB1 (Kvbeta1), KCNAB2 (Kvbeta2) and KCNAB3 (Kvbeta3).KCNAB3 associates with Kv1.5 alpha subunits, resulting in a much faster inactivation than is observed in kv1.5 channels formed from alpha subunitsalone []. KCNAB3 channels are expressed specifically in the brain, with most prominent expression in the cerebellum. Weaker expression is observed in the cortex, occipital lobe, frontal lobe and temporal lobe.
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers []. In eukaryotic cells, K+channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].All K+channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+channels; and three types of calcium (Ca)-activated K+channels (BK, IK and SK) []. The 2TM domain family comprises inward-rectifying K+channels. In addition, there are K+channel alpha-subunits that possess two P-domains. These are usually highly regulated K+selective leak channels.The KCNAB family (also known as the Kvbeta family) of voltage-dependent potassium channel beta subunits form complexes with the alpha subunits which can modify the properties of the channel. Four of these soluble beta subunits form a complex with four alpha subunit cytoplasmic (T1) regions. These subunits belong to the family of are NADPH-dependent aldo-keto reductases, and bind NADPH-cofactors in their active sites. Changes in the oxidoreductase activity appear to markedly influence the gating mode of Kv channels, since mutations to the catalytic residues in the active site lessen the inactivating activity of KCNAB []. The KCNAB family is further divided into 3 subfamilies: KCNAB1 (Kvbeta1), KCNAB2 (Kvbeta2) and KCNAB3 (Kvbeta3).KCNAB1 associates with Kv1.4 and Kv1.5 alpha subunits and appears to have an N-terminal sequence that is similar to the Kv1 channel inactivation gate.Thus, when KCNAB1 subunits associate, their N-termini appear to be able to substitute for alpha subunit inactivation gates []. Three isoforms of KCNAB1 exist, which are produced by alternative splicing of the N-terminal90 amino acids. KCNAB1 channels are expressed in brain (caudate nucleus,hippocampus, amygdala, subthalamic nucleus and thalamus) and heart.
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers []. In eukaryotic cells, K+channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].All K+channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+channels; and three types of calcium (Ca)-activated K+channels (BK, IK and SK) []. The 2TM domain family comprises inward-rectifying K+channels. In addition, there are K+channel alpha-subunits that possess two P-domains. These are usually highly regulated K+selective leak channels.The KCNAB family (also known as the Kvbeta family) of voltage-dependent potassium channel beta subunits form complexes with the alpha subunits which can modify the properties of the channel. Four of these soluble beta subunits form a complex with four alpha subunit cytoplasmic (T1) regions. These subunits belong to the family of are NADPH-dependent aldo-keto reductases, and bind NADPH-cofactors in their active sites. Changes in the oxidoreductase activity appear to markedly influence the gating mode of Kv channels, since mutations to the catalytic residues in the active site lessen the inactivating activity of KCNAB []. The KCNAB family is further divided into 3 subfamilies: KCNAB1 (Kvbeta1), KCNAB2 (Kvbeta2) and KCNAB3 (Kvbeta3).KCNAB2 associates with Kv1.4 alpha subunits; however, association has onlyvery modest effects on the gating of this channel []. Two isoforms of KCNAB2exist, which are produced by alternative splicing of amino acids 26-39.
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers []. In eukaryotic cells, K+channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].All K+channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+channels; and three types of calcium (Ca)-activated K+channels (BK, IK and SK) []. The 2TM domain family comprises inward-rectifying K+channels. In addition, there are K+channel alpha-subunits that possess two P-domains. These are usually highly regulated K+selective leak channels.2P-domain channels influence the resting membrane potential and as a result can control cell excitability. In addition, they pass K+in response to changes in membrane potential, and are also tightly regulated by molecular oxygen, GABA (gamma-aminobutyric acid), noradrenaline and serotonin.The first member of this family (TOK1), cloned from Saccharomyces cerevisiae [], ispredicted to have eight potential transmembrane (TM) helices. However,subsequently-cloned two P-domain family members from Drosophila andmammalian species are predicted to have only four TM segments. They areusually referred to as TWIK-related channels (Tandem of P-domains in a Weakly Inward rectifying K+ channel) [, , , ]. Functional characterisation of these channels has revealed a diversity of properties in that they may show inward or outward rectification, their activity may be modulated in different directions by protein phosphorylation, and their sensitivity to changes in intracellular or extracellular pH varies. Despite these disparate properties, they are all thought to share the same topology offour TM segments, including two P-domains. That TWIK-related K+ channelsall produce instantaneous and non-inactivating K+ currents, which do notdisplay a voltage-dependent activation threshold, suggests that they arebackground (leak) K+ channels involved in the generation and modulation of the resting membrane potential in various cell types. Further studies have revealed that they may be found in many species, including: plants, invertebrates and mammals.
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers []. In eukaryotic cells, K+channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].All K+channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+channels; and three types of calcium (Ca)-activated K+channels (BK, IK and SK) []. The 2TM domain family comprises inward-rectifying K+channels. In addition, there are K+channel alpha-subunits that possess two P-domains. These are usually highly regulated K+selective leak channels.KCNQ channels (also known as KQT-like channels) differ from other voltage-gated 6 TM helix channels, chiefly in that they possess no tetramerisation domain. Consequently, they rely on interaction with accessory subunits, or form heterotetramers with other members of the family []. Currently, 5 members of the KCNQ family are known. These have been found to be widely distributed within the body, having been shown to be expressed in the heart, brain, pancreas, lung, placenta and ear. They were initially cloned as a result of a search for proteins involved in cardiac arhythmia. Subsequently, mutations in other KCNQ family members have been shown to be responsible for some forms of hereditary deafness []and benign familial neonatal epilepsy [].KCNQ1 was the first member of the KCNQ channel family to be isolated, and has been found to be the most common cause of the disease `long QT syndrome' a cardiac arhythmia resulting in a prolonged QT interval. In exceptional cases, this can lead to sudden death, triggered by extreme stress [, ]. KCNQ1 is expressed in the stria vascularis of the inner ear, and may be the cause of hereditary deafness [].
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers []. In eukaryotic cells, K+channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].All K+channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+channels; and three types of calcium (Ca)-activated K+channels (BK, IK and SK) []. The 2TM domain family comprises inward-rectifying K+channels. In addition, there are K+channel alpha-subunits that possess two P-domains. These are usually highly regulated K+selective leak channels.Ca2+-activated K+ channels are a diverse group of channels that are activated by an increase in intracellular Ca2+ concentration. They are found in the majority of nerve cells, where they modulate cell excitability and action potential. Three types of Ca2+-activated K+ channel have been characterised, termed small-conductance (SK), intermediate conductance (IK) and large conductance (BK) respectively [].SK channels are thought to play an important role in the functioning of all excitable tissues. To date, 3 subtypes (designated SK1-SK3) have been cloned, each of which possesses a different tissue expression profile: SK1 channels are expressed in the heart; SK2 channels are found in the adrenal gland; and SK3 channels are known to be present in skeletal muscle []. SK channels have a single-channel conductance of 2-20 pS and are activated by rises in cytosolic calcium with half maximal activation in the 400-800 nM range [, ]. Unlike BK channels, they are voltage insensitive and unaffected by low concentrations of TEA, charybdotoxin, or iberiotoxin. However, they are potently blocked by the bee venom apamin [, ], tubocurarine, and quaternary salts of bicuculline [, ]. A new series of compounds that block SK channels include dequalinium
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers []. In eukaryotic cells, K+channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].All K+channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+channels; and three types of calcium (Ca)-activated K+channels (BK, IK and SK) []. The 2TM domain family comprises inward-rectifying K+channels. In addition, there are K+channel alpha-subunits that possess two P-domains. These are usually highly regulated K+selective leak channels.KCNQ channels (also known as KQT-like channels) differ from other voltage-gated 6 TM helix channels, chiefly in that they possess no tetramerisation domain. Consequently, they rely on interaction with accessory subunits, or form heterotetramers with other members of the family []. Currently, 5 members of the KCNQ family are known. These have been found to be widely distributed within the body, having been shown to be expressed in the heart, brain, pancreas, lung, placenta and ear. They were initially cloned as a result of a search for proteins involved in cardiac arhythmia. Subsequently, mutations in other KCNQ family members have been shown to be responsible for some forms of hereditary deafness []and benign familial neonatal epilepsy [].KCNQ4 gene maps to the DFNA2 locus for a form of nonsyndromic dominant deafness. In the cochlea, it is expressed in sensory outer hair cells [].
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers []. In eukaryotic cells, K+channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].All K+channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+channels; and three types of calcium (Ca)-activated K+channels (BK, IK and SK) []. The 2TM domain family comprises inward-rectifying K+channels. In addition, there are K+channel alpha-subunits that possess two P-domains. These are usually highly regulated K+selective leak channels.BK channels (also referred to as high-conductance, maxi-K channels or Slo family channels) []are widely expressed in the body, being found in glandular tissue, smooth and skeletal muscle, as well as in neural tissues. They have been demonstrated to regulate arteriolar and airway diameter, and also neurotransmitter release. Each channel complex is thought to be composed of 2 types of subunit; the pore-forming (alpha) subunits and smaller accessory (beta) subunits.The alpha subunit of the BK channel was initially thought to share the characteristic 6TM organisation of the voltage-gated K+ channels. However, the molecule is now thought to possess an additional TM domain, with an extracellular N terminus and intracellular C terminus. This C-terminal region contains 4 predominantly hydrophobic domains, which are also thought to lie intracellularly. The extracellular N terminus and the first TM region are required for modulation by the beta subunit. The precise location of the Ca2+-binding site that modulates channel activation remains unknown, but it is thought to lie within the C-terminal hydrophobic domains.The sodium-activated potassium channels Slick (Slo2.1, KCNT2) and Slack (Slo2.2, KCNT1) belong to the structurally related high-conductance potassium channels of the Slo family []. Slo3, also a member of the Slo family, is exclusively expressed in mammalian sperm [].
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers []. In eukaryotic cells, K+channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].All K+channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+channels; and three types of calcium (Ca)-activated K+channels (BK, IK and SK) []. The 2TM domain family comprises inward-rectifying K+channels. In addition, there are K+channel alpha-subunits that possess two P-domains. These are usually highly regulated K+selective leak channels.The first EAG K+ channel was identified in Drosophila melanogaster (Fruit fly), following a screen for mutations giving rise to behavioural abnormalities. Disruption of the Eag gene caused an ether-induced, leg-shaking behaviour. Subsequent studies have revealed a conserved multi-gene family of EAG-like K+ channels, which are present in human and many other species. Based on the varying functional properties of the channels, the family has been divided into 3 subfamilies: EAG, ELK and ERG. Interestingly, Caenorhabditis elegans appears to lack the ELK type [].Little is known about the properties of channels of the ELK subfamily. However, when expressed in frog oocytes, they show properties between thoseof the EAG and ERG subtypes. Included in this family are Bec1 and Bec2,brain-specific genes found in the human telencephalon regions. It is thoughtthat they are involved in cellular excitability of restricted neurons in thehuman central nervous system. Phylogenetic analysis reveals that these genesconstitute a subfamily with Elk within the Eag family []. Recently, afurther Elk subfamily member has been identified in the mouse (Melk). On thebasis of sequence similarity, this indicates a distinct subclass within this family [].
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers []. In eukaryotic cells, K+channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].All K+channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+channels; and three types of calcium (Ca)-activated K+channels (BK, IK and SK) []. The 2TM domain family comprises inward-rectifying K+channels. In addition, there are K+channel alpha-subunits that possess two P-domains. These are usually highly regulated K+selective leak channels.The Kv family can be divided into several subfamilies on the basis of sequence similarity and function. Four of these subfamilies, Kv1 (Shaker), Kv2 (Shab), Kv3 (Shaw) and Kv4 (Shal), consist of pore-forming alpha subunits that associate with different types of beta subunit. Each alpha subunit comprises six hydrophobic TM domains with a P-domain between the fifth and sixth, which partially resides in the membrane. The fourth TM domain has positively charged residues at every third residue and acts as a voltage sensor, which triggers the conformational change that opens the channel pore in response to a displacement in membrane potential []. More recently, 4 new electrically-silent alpha subunits have been cloned: Kv5 (KCNF), Kv6 (KCNG), Kv8 and Kv9 (KCNS). These subunits do not themselves possess any functional activity, but appear to form heteromeric channels with Kv2 subunits, and thus modulate Shab channel activity []. When highly expressed, they inhibit channel activity, but at lower levels show more specific modulatory actions.Coexpression of Kv6 subunits with Kv2 subunits has a slowing effect on Kv2 channel inactivation at strong depolarising potentials, but has little effect on channel inactivation at intermediate potentials [].
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others inresponse to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers []. In eukaryotic cells, K+channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].All K+channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+channels; and three types of calcium (Ca)-activated K+channels (BK, IK and SK) []. The 2TM domain family comprises inward-rectifying K+channels. In addition, there are K+channel alpha-subunits that possess two P-domains. These are usually highly regulated K+selective leak channels.The Kv family can be divided into several subfamilies on the basis of sequence similarity and function. Four of these subfamilies, Kv1 (Shaker), Kv2 (Shab), Kv3 (Shaw) and Kv4 (Shal), consist of pore-forming alpha subunits that associate with different types of beta subunit. Each alpha subunit comprises six hydrophobic TM domains with a P-domain between the fifth and sixth, which partially resides in the membrane. The fourth TM domain has positively charged residues at every third residue and acts as a voltage sensor, which triggers the conformational change that opens the channel pore in response to a displacement in membrane potential []. More recently, 4 new electrically-silent alpha subunits have been cloned: Kv5 (KCNF), Kv6 (KCNG), Kv8 and Kv9 (KCNS). These subunits do not themselves possess any functional activity, but appear to form heteromeric channels with Kv2 subunits, and thus modulate Shab channel activity []. When highly expressed, they inhibit channel activity, but at lower levels show more specific modulatory actions.Coexpression of Kv8 subunits with Kv2 subunits produces altered channel-activation kinetics that do not fit the standard model. In addition, channel inactivation shows a shift in voltage-dependence toward more negative potentials and a slower time course. TM domain 6 is thought to play a key role in these modulatory effects [].
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependentgating mechanism, channel conductance and toxin binding properties. Each type of K+channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers []. In eukaryotic cells, K+channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].All K+channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+channels; and three types of calcium (Ca)-activated K+channels (BK, IK and SK) []. The 2TM domain family comprises inward-rectifying K+channels. In addition, there are K+channel alpha-subunits that possess two P-domains. These are usually highly regulated K+selective leak channels.The Kv family can be divided into several subfamilies on the basis of sequence similarity and function. Four of these subfamilies, Kv1 (Shaker), Kv2 (Shab), Kv3 (Shaw) and Kv4 (Shal), consist of pore-forming alpha subunits that associate with different types of beta subunit. Each alpha subunit comprises six hydrophobic TM domains with a P-domain between the fifth and sixth, which partially resides in the membrane. The fourth TM domain has positively charged residues at every third residue and acts as a voltage sensor, which triggers the conformational change that opens the channel pore in response to a displacement in membrane potential []. More recently, 4 new electrically-silent alpha subunits have been cloned: Kv5 (KCNF), Kv6 (KCNG), Kv8 and Kv9 (KCNS). These subunits do not themselves possess any functional activity, but appear to form heteromeric channels with Kv2 subunits, and thus modulate Shab channel activity []. When highly expressed, they inhibit channel activity, but at lower levels show more specific modulatory actions.Coexpression of Kv9 subunits with Shab subunits produces a shift in the voltage-dependence of channel inactivation toward more negative potentials []. In addition, Shab channel deactivation and inactivation are slowed, and the single channel conductance is increased [].
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers []. In eukaryotic cells, K+channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].All K+channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+channels; and three types of calcium (Ca)-activated K+channels (BK, IK and SK) []. The 2TM domain family comprises inward-rectifying K+channels. In addition, there are K+channel alpha-subunits that possess two P-domains. These are usually highly regulated K+selective leak channels.Ca2+-activated K+ channels are a diverse group of channels that are activated by an increase in intracellular Ca2+ concentration. They are found in the majority of nerve cells, where they modulate cell excitability and action potential. Three types of Ca2+-activated K+ channel have been characterised, termed small-conductance (SK), intermediate conductance (IK) and large conductance (BK) respectively [].BK channels (also referred to as maxi-K channels) are widely expressed in the body, being found in glandular tissue, smooth and skeletal muscle, as well as in neural tissues. They have been demonstrated to regulate arteriolar and airway diameter, and also neurotransmitter release. Eachchannel complex is thought to be composed of 2 types of subunit: the pore-forming (alpha) subunits and smaller accessory (beta) subunits.The beta subunit (which is thought to possess 2 TM domains) increases theCa2+ sensitivity of the BK channel []. It does this by enhancing the timespent by the channel in burst-like open states. However, it has little effect on the durations of closed intervals between bursts, or on thenumbers of open and closed states entered during gating [].
Potassium channels are the most diverse group of the ion channel family [, ]. Theyare important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers []. In eukaryotic cells, K+channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].All K+channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+channels; and three types of calcium (Ca)-activated K+channels (BK, IK and SK) []. The 2TM domain family comprises inward-rectifying K+channels. In addition, there are K+channel alpha-subunits that possess two P-domains. These are usually highly regulated K+selective leak channels.KCNQ channels (also known as KQT-like channels) differ from other voltage-gated 6 TM helix channels, chiefly in that they possess no tetramerisation domain. Consequently, they rely on interaction with accessory subunits, or form heterotetramers with other members of the family []. Currently, 5 members of the KCNQ family are known. These have been found to be widely distributed within the body, having been shown to be expressed in the heart, brain, pancreas, lung, placenta and ear. They were initially cloned as a result of a search for proteins involved in cardiac arhythmia. Subsequently, mutations in other KCNQ family members have been shown to be responsible for some forms of hereditary deafness []and benign familial neonatal epilepsy [].The KCNQ2 channel subunit is thought to form active channels by hetero- tetramerisation with KCNQ3, although some K+ channel activity does results from the expression of KCNQ2 alone []. Channel function is modulated by phosphorylation, since experiments have demonstrated that an increase in intracellular cAMP concentration can enhance channel activity. Frameshift mutations in both KCNQ2 and KCNQ3 are associated with benign familial neonatal epilepsy [], a disorder where an infant begins to suffer convulsions, within the first three days of life. These symptoms usually disappear after approximately three months, but affected individuals have a higher than average chance of subsequently developing epilepsy (10-15%), in later life [].
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers []. In eukaryotic cells, K+channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].All K+channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+channels; and three types of calcium (Ca)-activated K+channels (BK, IK and SK) []. The 2TM domain family comprises inward-rectifying K+channels. In addition, there are K+channel alpha-subunits that possess two P-domains. These are usually highly regulated K+selective leak channels.KCNQ channels (also known as KQT-like channels) differ from other voltage-gated 6 TM helix channels, chiefly in that they possess no tetramerisation domain. Consequently, they rely on interaction with accessory subunits, or form heterotetramers with other members of the family []. Currently, 5 members of the KCNQ family are known. These have been found to be widely distributed within the body, having been shown to be expressed in the heart, brain, pancreas, lung, placenta and ear. They were initially cloned as a result of a search for proteins involved in cardiac arhythmia. Subsequently, mutations in other KCNQ family members have been shown to be responsible for some forms of hereditary deafness []and benign familial neonatal epilepsy [].The KCNQ3 channel subunit is thought to form active channels by hetero- tetramerisation with KCNQ2, although some K+ channel activity does result from the expression of KCNQ3 alone []. Channel function is modulated by phosphorylation; experiments have demonstrated that an increase in intracellular cAMP concentration can enhance channel activity. Frameshift mutations in both KCNQ2 and KCNQ3 are associated with benign familial neonatal epilepsy [], a disorder in which infants suffer convulsions within the first 3 days of life. These symptoms usually disappear after about 3 months, but affected individuals have a higher than average chance of subsequently developing epilepsy (10-15%) in later life [].
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers []. In eukaryotic cells, K+channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].All K+channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+channels; and three types of calcium (Ca)-activated K+channels (BK, IK and SK) []. The 2TM domain family comprises inward-rectifying K+channels. In addition, there are K+channel alpha-subunits that possess two P-domains. These are usually highly regulated K+selective leak channels.Inwardly-rectifying potassium channels (Kir) are the principal class of two-TM domain potassium channels. They are characterised by the property of inward-rectification, which is described as the ability to allow large inward currents and smaller outward currents. Inwardly rectifying potassium channels (Kir) are responsible for regulating diverse processes including: cellular excitability, vascular tone, heart rate, renal salt flow, and insulin release []. To date, around twenty members of this superfamily have been cloned, which can be grouped into six families by sequence similarity, and these are designated Kir1.x-6.x [, ].Cloned Kir channel cDNAs encode proteins of between ~370-500 residues, both N- and C-termini are thought to be cytoplasmic, and the N terminus lacks a signal sequence. Kir channel alpha subunits possess only 2TM domains linked with a P-domain. Thus, Kir channels share similarity with the fifth and sixth domains, and P-domain of the other families. It is thought that four Kir subunits assemble to form a tetrameric channel complex, which may be hetero- or homomeric [].This metazoan domain is found to the N terminus of Inward rectifier potassium channels (KIR2 or IRK2).
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers []. In eukaryotic cells, K+channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].All K+channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+channels; and three types of calcium (Ca)-activated K+channels (BK, IK and SK) []. The 2TM domain family comprises inward-rectifying K+channels. In addition, there are K+channel alpha-subunits that possess two P-domains. These are usually highly regulated K+selective leak channels.Inwardly-rectifying potassium channels (Kir) are the principal class of two-TM domain potassium channels. They are characterised by the property of inward-rectification, which is described as the ability to allowlarge inward currents and smaller outward currents. Inwardly rectifying potassium channels (Kir) are responsible for regulating diverse processes including: cellular excitability, vascular tone, heart rate, renal salt flow, and insulin release []. To date, around twenty members of this superfamily have been cloned, which can be grouped into six families by sequence similarity, and these are designated Kir1.x-6.x [, ].Cloned Kir channel cDNAs encode proteins of between ~370-500 residues, both N- and C-termini are thought to be cytoplasmic, and the N terminus lacks a signal sequence. Kir channel alpha subunits possess only 2TM domains linked with a P-domain. Thus, Kir channels share similarity with the fifth and sixth domains, and P-domain of the other families. It is thought that four Kir subunits assemble to form a tetrameric channel complex, which may be hetero- or homomeric [].
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers []. In eukaryotic cells, K+channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].All K+channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+channels; and three types of calcium (Ca)-activated K+channels (BK, IK and SK) []. The 2TM domain family comprises inward-rectifying K+channels. In addition, there areK+channel alpha-subunits that possess two P-domains. These are usually highly regulated K+selective leak channels.KCNQ channels (also known as KQT-like channels) differ from other voltage-gated 6 TM helix channels, chiefly in that they possess no tetramerisation domain. Consequently, they rely on interaction with accessory subunits, or form heterotetramers with other members of the family []. Currently, 5 members of the KCNQ family are known. These have been found to be widely distributed within the body, having been shown to be expressed in the heart, brain, pancreas, lung, placenta and ear. They were initially cloned as a result of a search for proteins involved in cardiac arhythmia. Subsequently, mutations in other KCNQ family members have been shown to be responsible for some forms of hereditary deafness []and benign familial neonatal epilepsy [].This entry represents a region found at the C terminus of these proteins.
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers []. In eukaryotic cells, K+channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].All K+channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+channels; and three types of calcium (Ca)-activated K+channels (BK, IK and SK) []. The 2TM domain family comprises inward-rectifying K+channels. In addition, there are K+channel alpha-subunits that possess two P-domains. These are usually highly regulated K+selective leak channels.The Kv family can be divided into several subfamilies on the basis of sequence similarity and function. Four of these subfamilies, Kv1 (Shaker), Kv2 (Shab), Kv3 (Shaw) and Kv4 (Shal), consist of pore-forming alpha subunits that associate with different types of beta subunit. Each alpha subunit comprises six hydrophobic TM domains with a P-domain between the fifth and sixth, which partially resides in the membrane. The fourth TM domain has positively charged residues at every third residue and acts as a voltage sensor, which triggers the conformational change that opens the channel pore in response to a displacement in membrane potential []. More recently, 4 new electrically-silent alpha subunits have been cloned: Kv5 (KCNF), Kv6 (KCNG), Kv8 and Kv9 (KCNS). These subunits do not themselves possess any functional activity, but appear to form heteromeric channels with Kv2 subunits, and thus modulate Shab channel activity []. When highly expressed, they inhibit channel activity, but at lower levels show more specific modulatory actions.The first Kv1 sequence (also known as Shaker) was found in Drosophila melanogaster (Fruit fly). Several vertebrate potassium channels with similar amino acid sequences were subsequently found and, together with the D. melanogaster Shaker channel, now constitute the Kv1 family. The family consists of at least 6 genes (Kv1.1, Kv1.2, Kv1.3, Kv1.4, Kv1.5 and Kv1.6) which each play distinct physiological roles. A conserved motif found towards the C terminus of these channels is required for efficient processing and surface expression []. Variations in this motif account for the differences in cell surface expression and localisation between family members. These channels are mostly expressed in the brain, but can also be found in non-excitable cells, such as lymphocytes []. Kv1.2 channels are uniformly distributed in the heart and brain. They play diverse functional roles in several neuronal compartments, especially in the regulation of pre- and post-synaptic membrane excitability. Kv1.2 subunits can co-localise with other Kv1 subunits. For example, Kv1.2 colocalises with Kv1.1 in the nodes of Ranvier in myelinated axons, and in the brain, in particular, the axons and nerve terminals; Kv1.2 coassembles with Kv1.4 subunits. In addition, Kv1.2 assembles with the Kv-beta2 subunit resulting in the promotion of Kv1.2 transport to the cell surface.
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers []. In eukaryotic cells, K+channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].All K+channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+channels; and three types of calcium (Ca)-activated K+channels (BK, IK and SK) []. The 2TM domain family comprises inward-rectifying K+channels. In addition, there are K+channel alpha-subunits that possess two P-domains. These are usually highly regulated K+selective leak channels.The Kv family can be divided into several subfamilies on the basis of sequence similarity and function. Four of these subfamilies, Kv1 (Shaker), Kv2 (Shab), Kv3 (Shaw) and Kv4 (Shal), consist of pore-forming alpha subunits that associate with different types of beta subunit. Each alpha subunit comprises six hydrophobic TM domains with a P-domain between the fifth and sixth, which partially resides in the membrane. The fourth TM domain has positively charged residues at every third residue and acts as a voltage sensor, which triggers the conformational change that opens the channel pore in response to a displacement in membrane potential []. More recently, 4 new electrically-silent alpha subunits have been cloned: Kv5 (KCNF), Kv6 (KCNG), Kv8 and Kv9 (KCNS). These subunits do not themselves possess any functional activity, but appear to form heteromeric channels with Kv2 subunits, and thus modulate Shab channel activity []. When highly expressed, they inhibit channel activity, but at lower levels show more specific modulatory actions.The first Kv1 sequence (also known as Shaker) was found in Drosophila melanogaster (Fruit fly). Several vertebrate potassium channels with similar amino acid sequences were subsequently found and, together with the D. melanogaster Shaker channel, now constitute the Kv1 family. The family consists of at least 6 genes (Kv1.1, Kv1.2, Kv1.3, Kv1.4, Kv1.5 and Kv1.6) which each play distinct physiological roles. A conserved motif found towards the C terminus of these channels is required for efficient processing and surface expression []. Variations in this motif account for the differences in cell surface expression and localisation between family members. These channels are mostly expressed in the brain, but can also be found in non-excitable cells, such as lymphocytes []. This entry represents the Kv1 group of voltage-dependent potassium channels.
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers []. In eukaryotic cells, K+channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].All K+channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+channels; and three types of calcium (Ca)-activated K+channels (BK, IK and SK) []. The 2TM domain family comprises inward-rectifying K+channels. In addition, there are K+channel alpha-subunits that possess two P-domains. These are usually highly regulated K+selective leak channels.The Kv family can be divided into several subfamilies on the basis of sequence similarity and function. Four of these subfamilies, Kv1 (Shaker), Kv2 (Shab), Kv3 (Shaw) and Kv4 (Shal), consist of pore-forming alpha subunits that associate with different types of beta subunit. Each alpha subunit comprises six hydrophobic TM domains with a P-domain between the fifth and sixth, which partially resides in the membrane. The fourth TM domain has positively charged residues at every third residue and acts as a voltage sensor, which triggers the conformational change that opens the channel pore in response to a displacement in membrane potential []. More recently, 4 new electrically-silent alpha subunits have been cloned: Kv5 (KCNF), Kv6 (KCNG), Kv8 and Kv9 (KCNS). These subunits do not themselves possess any functional activity, but appear to form heteromeric channels with Kv2 subunits, and thus modulate Shab channel activity []. When highly expressed, they inhibit channel activity, but at lower levels show more specific modulatory actions.The first Kv1 sequence (also known as Shaker) was found in Drosophila melanogaster (Fruit fly). Several vertebrate potassium channels with similar amino acid sequences were subsequently found and, together with the D. melanogaster Shaker channel, now constitute the Kv1 family. The family consists of at least 6 genes (Kv1.1, Kv1.2, Kv1.3, Kv1.4, Kv1.5 and Kv1.6) which each play distinct physiological roles. A conserved motif found towards the C terminus of these channels is required for efficient processing and surface expression []. Variations in this motif account for the differences in cell surface expression and localisation between family members. These channels are mostly expressed in the brain, but can also be found in non-excitable cells, such as lymphocytes []. The Kv1.1 subfamily is expressed in the embryonic nervous system, brain andlymphoid thymocyte precursors. The Kv1.1 subunits can associate with Kv1.2 and Kv1.4 subunits, especially in the cerebellum. Point mutations in Kv1.1 result in the disruption of this association and episodic ataxia type I, a rare autosomal dominant neurological disorder characterised by brief episodes of ataxia [].
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers []. In eukaryotic cells, K+channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].All K+channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+channels; and three types of calcium (Ca)-activated K+channels (BK, IK and SK) []. The 2TM domain family comprises inward-rectifying K+channels. In addition, there are K+channel alpha-subunits that possess two P-domains. These are usually highly regulated K+selective leak channels.The Kv family can be divided into several subfamilies on the basis of sequence similarity and function. Four of these subfamilies, Kv1 (Shaker), Kv2 (Shab), Kv3 (Shaw) and Kv4 (Shal), consist of pore-forming alpha subunits that associate with different types of beta subunit. Each alpha subunit comprises six hydrophobic TM domains with a P-domain between the fifth and sixth, which partially resides in the membrane. The fourth TM domain has positively charged residues at every third residue and acts as a voltage sensor, which triggers the conformational change that opens the channel pore in response to a displacement in membrane potential []. More recently, 4 new electrically-silent alpha subunits have been cloned: Kv5 (KCNF), Kv6 (KCNG), Kv8 and Kv9 (KCNS). These subunits do not themselves possess any functional activity, but appear to form heteromeric channels with Kv2 subunits, and thus modulate Shab channel activity []. When highly expressed, they inhibit channel activity, but at lower levels show more specific modulatory actions.The Shal potassium channel was found in Drosophila melanogaster (Fruit fly). Several vertebrate potassium channels with similar amino acid sequences were subsequently found and, together with the D. melanogaster Shal channel, now constitute the Kv4 family. These channels are the primary subunits contributing to transient, voltage-dependent potassium currents in the nervous system (A currents) and the heart (transient outward current), and are inhibited by free fatty acids []. This family can be further divided into 3 subfamilies, designated Kv4.1(KCND1), Kv4.2(KCND2) and Kv4.3(KCND3).Kv4.1 channels are expressed in the heart, brain, liver, kidney and pancreas. Association with specific subunits increases their surface expression. Essential to their function are the N and C termini, which work together to control the inactivation of these channels.
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers []. In eukaryotic cells, K+channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].All K+channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+selectivity sequence. In families that contain one P-domain, four subunits assemble to form aselective pathway for K+across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+channels; and three types of calcium (Ca)-activated K+channels (BK, IK and SK) []. The 2TM domain family comprises inward-rectifying K+channels. In addition, there are K+channel alpha-subunits that possess two P-domains. These are usually highly regulated K+selective leak channels.The Kv family can be divided into several subfamilies on the basis of sequence similarity and function. Four of these subfamilies, Kv1 (Shaker), Kv2 (Shab), Kv3 (Shaw) and Kv4 (Shal), consist of pore-forming alpha subunits that associate with different types of beta subunit. Each alpha subunit comprises six hydrophobic TM domains with a P-domain between the fifth and sixth, which partially resides in the membrane. The fourth TM domain has positively charged residues at every third residue and acts as a voltage sensor, which triggers the conformational change that opens the channel pore in response to a displacement in membrane potential []. More recently, 4 new electrically-silent alpha subunits have been cloned: Kv5 (KCNF), Kv6 (KCNG), Kv8 and Kv9 (KCNS). These subunits do not themselves possess any functional activity, but appear to form heteromeric channels with Kv2 subunits, and thus modulate Shab channel activity []. When highly expressed, they inhibit channel activity, but at lower levels show more specific modulatory actions.The Shal potassium channel was found in Drosophila melanogaster (Fruit fly). Several vertebrate potassium channels with similar amino acid sequences were subsequently found and, together with the D. melanogaster Shal channel, now constitute the Kv4 family. These channels are the primary subunits contributing to transient, voltage-dependent potassium currents in the nervous system (A currents) and the heart (transient outward current), and are inhibited by free fatty acids []. This family can be further divided into 3 subfamilies, designated Kv4.1(KCND1), Kv4.2(KCND2) and Kv4.3(KCND3).Kv4.2 channels are the major contributors to somatodendritic A-type potassium channels in the basal ganglia and basal forebrain neurons []. They are also expressed in the heart and CNS. In rodents, they are an important constituent of the cardiac transient outward current, Ito. In addition, they have a predicted role in regulating neuronal transmission at post-synaptic loci in defined brain regions. Kv4.2 channels contain a number of conserved sites for mitogen-activated protein kinase ERK phosphorylation, suggesting that ERK may regulate potassium channel function by direct phosphorylation [].
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers []. In eukaryotic cells, K+channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].All K+channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+channels; and three types of calcium (Ca)-activated K+channels (BK, IK and SK) []. The 2TM domain family comprises inward-rectifying K+channels. In addition, there are K+channel alpha-subunits that possess two P-domains. These are usually highly regulated K+selective leak channels.The Kv family can be divided into several subfamilies on the basis of sequence similarity and function. Four of these subfamilies, Kv1 (Shaker), Kv2 (Shab), Kv3 (Shaw) and Kv4 (Shal), consist of pore-forming alpha subunits that associate with different types of beta subunit. Each alpha subunit comprises six hydrophobic TM domains with a P-domain between the fifth and sixth, which partially resides in the membrane. The fourth TM domain has positively charged residues at every third residue and acts as a voltage sensor, which triggers the conformational change that opens the channel pore in response to a displacement in membrane potential []. More recently, 4 new electrically-silent alpha subunits have been cloned: Kv5 (KCNF), Kv6 (KCNG), Kv8 and Kv9 (KCNS). These subunits do not themselves possess any functional activity, but appear to form heteromeric channels with Kv2 subunits, and thus modulate Shab channel activity []. When highly expressed, they inhibit channel activity, but at lower levels show more specific modulatory actions.The first Kv1 sequence (also known as Shaker) was found in Drosophila melanogaster (Fruit fly). Several vertebrate potassium channels with similar amino acid sequences were subsequently found and, together with the D. melanogaster Shaker channel, now constitute the Kv1 family. The family consists of at least 6 genes (Kv1.1, Kv1.2, Kv1.3, Kv1.4, Kv1.5 and Kv1.6) which each play distinct physiological roles. A conserved motif found towards the C terminus of these channels is required for efficient processing and surface expression []. Variations in this motif account for the differences in cell surface expression and localisation between family members. These channels are mostly expressed in the brain, but can also be found in non-excitable cells, such as lymphocytes []. Kv1.5 channels are expressed in the heart and pancreatic beta-cells. Themost studied is the human Kv1.5 channel (hKv1.5), which is thought to underlie the ultra-rapidly activating delayed rectifier K+current Ikur found in human atrial myocytes []. It is also expressed in the human ventricle where it is possible that it contributes to the K+current through formation of heteromultimeric K+channels with other Kv-alpha subunits []. Further experiments have shown that it is regulated by extracellular potassium and pH [].
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers []. In eukaryotic cells, K+channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].All K+channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+channels; and three types of calcium (Ca)-activated K+channels (BK, IK and SK) []. The 2TM domain family comprises inward-rectifying K+channels. In addition, there are K+channel alpha-subunits that possess two P-domains. These are usually highly regulated K+selective leak channels.The Kv family can be divided into several subfamilies on the basis of sequence similarity and function. Four of these subfamilies, Kv1 (Shaker), Kv2 (Shab), Kv3 (Shaw) and Kv4 (Shal), consist of pore-forming alpha subunits that associate with different types of beta subunit. Each alpha subunit comprises six hydrophobic TM domains with a P-domain between the fifth and sixth, which partially resides in the membrane. The fourth TM domain has positively charged residues at every third residue and acts as a voltage sensor, which triggers the conformational change that opens the channel pore in response to a displacement in membrane potential []. More recently, 4 new electrically-silent alpha subunits have been cloned: Kv5 (KCNF), Kv6 (KCNG), Kv8 and Kv9 (KCNS). These subunits do not themselves possess any functional activity, but appear to form heteromeric channels with Kv2 subunits, and thus modulate Shab channel activity []. When highly expressed, they inhibit channelactivity, but at lower levels show more specific modulatory actions.The first Kv1 sequence (also known as Shaker) was found in Drosophila melanogaster (Fruit fly). Several vertebrate potassium channels with similar amino acid sequences were subsequently found and, together with the D. melanogaster Shaker channel, now constitute the Kv1 family. The family consists of at least 6 genes (Kv1.1, Kv1.2, Kv1.3, Kv1.4, Kv1.5 and Kv1.6) which each play distinct physiological roles. A conserved motif found towards the C terminus of these channels is required for efficient processing and surface expression []. Variations in this motif account for the differences in cell surface expression and localisation between family members. These channels are mostly expressed in the brain, but can also be found in non-excitable cells, such as lymphocytes []. KCNA6is expressed in the heart, smooth muscle cells and brain, especiallythe midbrain areas and brainstem. The KCNA6 alpha-subunits can also coassemble with other Shaker alpha subunits, for example, with Kv1.5 to form heteromultimeric K+channels.
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers []. In eukaryotic cells, K+channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].All K+channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+channels; and three types of calcium (Ca)-activated K+channels (BK, IK and SK) []. The 2TM domain family comprises inward-rectifying K+channels. In addition, there are K+channel alpha-subunits that possess two P-domains. These are usually highly regulated K+selective leak channels.The Kv family can be divided into several subfamilies on the basis of sequence similarity and function. Four of these subfamilies, Kv1 (Shaker), Kv2 (Shab), Kv3 (Shaw) and Kv4 (Shal), consist of pore-forming alpha subunits that associate with different types of beta subunit. Each alpha subunit comprises six hydrophobic TM domains with a P-domain between the fifth and sixth, which partially resides in the membrane. The fourth TM domain has positively charged residues at every third residue and acts as a voltage sensor, which triggers the conformational change that opens the channel pore in response to a displacement in membrane potential []. More recently, 4 new electrically-silent alpha subunits have been cloned: Kv5 (KCNF), Kv6 (KCNG), Kv8 and Kv9 (KCNS). These subunits do not themselves possess any functional activity, but appear to form heteromeric channels with Kv2 subunits, and thus modulate Shab channel activity []. When highly expressed, they inhibit channel activity, but at lower levels show more specific modulatory actions.The first Kv1 sequence (also known as Shaker) was found in Drosophila melanogaster (Fruit fly). Several vertebrate potassium channels with similar amino acid sequences were subsequently found and, together with the D. melanogaster Shaker channel, now constitute the Kv1 family. The family consists of at least 6 genes (Kv1.1, Kv1.2, Kv1.3, Kv1.4, Kv1.5 and Kv1.6) which each play distinct physiological roles. A conserved motif found towards the C terminus of these channels is required for efficient processing and surface expression []. Variations in this motif account for the differences in cell surface expression and localisation between family members. These channels are mostly expressed in the brain, but can also be found in non-excitable cells, such as lymphocytes []. Kv1.3 subunits are expressed in T-lymphocytes, microglia and osteoclasts. In activated T-lymphocytes, they maintain the secretion of the lymphokineIL-2. They are also believed to be responsible for the decrease in regulatory volume in response to hypotonic shock, and a Kv1.3 homologue has predicted roles in renal medullary K+transport.
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers []. In eukaryotic cells, K+channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].All K+channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+channels; and three types of calcium (Ca)-activated K+channels (BK, IK and SK) []. The 2TM domain family comprises inward-rectifying K+channels. In addition, there are K+channel alpha-subunits that possess two P-domains. These are usually highly regulated K+selective leak channels.The Kv family can be divided into several subfamilies on the basis of sequence similarity and function. Four of these subfamilies, Kv1 (Shaker), Kv2 (Shab), Kv3 (Shaw) and Kv4 (Shal), consist of pore-forming alpha subunits that associate with different types of beta subunit. Each alpha subunit comprises six hydrophobic TM domains with a P-domain between the fifth and sixth, which partially resides in the membrane. The fourth TM domain has positively charged residues at every third residue and acts as a voltage sensor, which triggers the conformational change that opens the channel pore in response to a displacement in membrane potential []. More recently, 4 new electrically-silent alpha subunits have been cloned: Kv5 (KCNF), Kv6 (KCNG), Kv8 and Kv9 (KCNS). These subunits do not themselves possess any functional activity, but appear to form heteromeric channels with Kv2 subunits, and thus modulate Shab channel activity []. When highly expressed, they inhibit channel activity, but at lower levels show more specific modulatory actions.The Shal potassium channel was found in Drosophila melanogaster (Fruit fly). Several vertebrate potassium channels with similar amino acid sequences were subsequently found and, together with the D. melanogaster Shal channel, now constitute the Kv4 family. These channels are the primary subunits contributing to transient, voltage-dependent potassium currents in the nervous system (A currents) and the heart (transient outward current), and are inhibited by free fatty acids []. This family can be further divided into 3 subfamilies, designated Kv4.1(KCND1), Kv4.2(KCND2) and Kv4.3(KCND3).Two isoforms of Kv4.3 have been cloned: one is full length and the other hasa small amino acid deletion. Both forms are expressed in the brain, whereasin the heart only the longer isoform is found []. Kv4.3 channels may have an important role in damping synaptic and excitatory membrane potentials. In the brain, they can also associate with Kv-beta2 subunits via the C terminus, resulting in increased channel density and protein expression [].
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers []. In eukaryotic cells, K+channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].All K+channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+channels; and three types of calcium (Ca)-activated K+channels (BK, IK and SK) []. The 2TM domain family comprises inward-rectifying K+channels. In addition, there are K+channel alpha-subunits that possess two P-domains. These are usually highly regulated K+selective leak channels.The Kv family can be divided into several subfamilies on the basis of sequence similarity and function. Four of these subfamilies, Kv1 (Shaker), Kv2 (Shab), Kv3 (Shaw) and Kv4 (Shal), consist of pore-forming alpha subunits that associate with different types of beta subunit. Each alpha subunit comprises six hydrophobic TM domains with a P-domain between the fifth and sixth, which partially resides in the membrane. The fourth TM domain has positively charged residues at every third residue and acts as a voltage sensor, which triggers the conformational change that opens the channel pore in response to a displacement in membrane potential []. More recently, 4 new electrically-silent alpha subunits have been cloned: Kv5 (KCNF), Kv6 (KCNG), Kv8 and Kv9 (KCNS). These subunits do not themselves possess any functional activity, but appear to form heteromeric channels with Kv2 subunits, and thus modulate Shab channel activity []. When highly expressed, they inhibit channel activity, but at lower levels show more specific modulatory actions.The Kv2 voltage-dependent potassium channels (also known as the Shab family) are responsible for much of the delayed rectifier current in Drosophila melanogaster (Fruit fly) nervous system and muscle.However, in vertebrates, Kv2 channels have been shwon to be involved in the delayed rectifier currents of the heart and skeletal muscles. They are also thought to be important in determining intrinsic neuronal excitability in both mammals and non-mammals []. Kv2 channels can be further divided into 2 subtypes, designated Kv2.1 and Kv2.2.Kv2.1 channels are expressed in the neurons. Essential for their function is protein phosphorylation dependent on protein kinase A. Three isoforms exhibiting temporal patterning during neuronal development have also been discovered, implying distinct roles for these channels in development.
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers []. In eukaryotic cells, K+channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].All K+channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+channels; and three types of calcium (Ca)-activated K+channels (BK, IK and SK) []. The 2TM domain family comprises inward-rectifying K+channels. In addition, there are K+channel alpha-subunits that possess two P-domains. These are usually highly regulated K+selective leak channels.Inwardly-rectifying potassium channels (Kir) are the principal class of two-TM domain potassium channels. They are characterised by the property of inward-rectification, which is described as the ability to allow large inward currents and smaller outward currents. Inwardly rectifying potassium channels (Kir) are responsible for regulating diverse processes including: cellular excitability, vascular tone, heart rate, renal salt flow, and insulin release []. To date, around twenty members of this superfamily have been cloned, which can be grouped into six families by sequence similarity, and these are designated Kir1.x-6.x [, ].Cloned Kir channel cDNAs encode proteins of between ~370-500 residues, both N- and C-termini are thought to be cytoplasmic, and the N terminus lacks a signal sequence. Kir channel alpha subunits possess only 2TM domains linked with a P-domain. Thus, Kir channels share similarity with the fifth and sixth domains, and P-domain of the other families. It is thought that four Kir subunits assemble to form a tetrameric channel complex, which may be hetero- or homomeric [].Kir6.x inward rectifier K+ channel family subunits associate withsulphonylurea receptors (SURs) to form ATP-sensitive K+(KATP) channels. These are octameric complexes containing equal numbers of Kir and SURsubunits. The resulting channels are regulated by cytosolic nucleotides,such as ATP, and thus link cell metabolism to electrical activity, and K+fluxes. They are important in the regulation of insulin secretion, the control of vascular and smooth muscle tone, and the response of the heart(and possibly the brain) to ischaemia.Channels formed by the association of Kir6.1 (also known as u-KATP-1) withthe SUR2B receptor are sensitive to K+channel-opening drugs such as diazoxide and pinacidil, closely resembling the properties of nativechannels found in vascular tissues [].
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers []. In eukaryotic cells, K+channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].All K+channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+channels; and three types of calcium (Ca)-activated K+channels (BK, IK and SK) []. The 2TM domain family comprises inward-rectifying K+channels. In addition, there are K+channel alpha-subunits that possess two P-domains. These are usually highly regulated K+selective leak channels.Inwardly-rectifying potassium channels (Kir) are the principal class of two-TM domain potassium channels. They are characterised by the property of inward-rectification, which is described as the ability to allow large inward currents and smaller outward currents. Inwardly rectifying potassium channels (Kir) are responsible for regulating diverse processes including: cellular excitability, vascular tone, heart rate, renal salt flow, and insulin release []. To date, around twenty members of this superfamily have been cloned, which can be grouped into six families by sequence similarity, and these are designated Kir1.x-6.x [, ].Cloned Kir channel cDNAs encode proteins of between ~370-500 residues, both N- and C-termini are thought to be cytoplasmic, and the N terminus lacks a signal sequence. Kir channel alpha subunits possess only 2TM domains linked with a P-domain. Thus, Kir channels share similarity with the fifth and sixth domains, and P-domain of the other families. It is thought that four Kir subunits assemble to form a tetrameric channel complex, which may be hetero- or homomeric [].Kir6.x inward rectifier K+ channel family subunits associate withsulphonylurea receptors (SURs) to form ATP-sensitive K+(KATP) channels. These are octameric complexes containing equal numbers of Kir and SURsubunits. The resulting channels are regulated by cytosolic nucleotides,such as ATP, and thus link cell metabolism to electrical activity, and K+fluxes. They are important in the regulation of insulin secretion, the control of vascular and smooth muscle tone, and the response of the heart(and possibly the brain) to ischaemia.Kir6.2 (also known as BIR/KATP) is thought to associate with SUR1 to formthe pancreatic beta cell KATP channel that is involved in regulation ofinsulin secretion. Combination of Kir6.2 with splice variants of SUR2 isthought to produce the cardiac and smooth muscle KATP isoforms [].
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers []. In eukaryotic cells, K+channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].All K+channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+channels; and three types of calcium (Ca)-activatedK+channels (BK, IK and SK) []. The 2TM domain family comprises inward-rectifying K+channels. In addition, there are K+channel alpha-subunits that possess two P-domains. These are usually highly regulated K+selective leak channels.Inwardly-rectifying potassium channels (Kir) are the principal class of two-TM domain potassium channels. They are characterised by the property of inward-rectification, which is described as the ability to allow large inward currents and smaller outward currents. Inwardly rectifying potassium channels (Kir) are responsible for regulating diverse processes including: cellular excitability, vascular tone, heart rate, renal salt flow, and insulin release []. To date, around twenty members of this superfamily have been cloned, which can be grouped into six families by sequence similarity, and these are designated Kir1.x-6.x [, ].Cloned Kir channel cDNAs encode proteins of between ~370-500 residues, both N- and C-termini are thought to be cytoplasmic, and the N terminus lacks a signal sequence. Kir channel alpha subunits possess only 2TM domains linked with a P-domain. Thus, Kir channels share similarity with the fifth and sixth domains, and P-domain of the other families. It is thought that four Kir subunits assemble to form a tetrameric channel complex, which may be hetero- or homomeric [].Kir1.3 (also known as Kir4.2) was cloned from human kidney, where it appearsto be found most abundantly. At lower levels, it has also been detected inthe pancreas and lung. It is most closely related to Kir1.2, to which it is62% identical. Unlike the other Kir1.x family members, in the Kir1.3sequence, the Walker Type A consensus motif (for nucleotide binding) isnot conserved. Heterologous expression of Kir1.3 in Xenopus oocytes did notlead to detectable channel activity. Indeed, co-expression of Kir1.3 witheither Kir1.1 or Kir1.2 reduced currents resulting from expression of theseinward rectifier subunits alone, consistent with a dominant negativeinfluence of Kir1.3 on Kir1.1 and Kir1.2 expression [].
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers []. In eukaryotic cells, K+channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].All K+channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+channels; and three types of calcium (Ca)-activated K+channels (BK, IK and SK) []. The 2TM domain family comprises inward-rectifying K+channels. In addition, there are K+channel alpha-subunits that possess two P-domains. These are usually highly regulated K+selective leak channels.Inwardly-rectifying potassium channels (Kir) are the principal class of two-TM domain potassium channels. They are characterised by the property of inward-rectification, which is described as the ability to allow large inward currents and smaller outward currents. Inwardly rectifying potassium channels (Kir) are responsible for regulating diverse processes including: cellular excitability, vascular tone, heart rate, renal salt flow, and insulin release []. To date, around twenty members of this superfamily have been cloned, which can be grouped into six families by sequence similarity, and these are designated Kir1.x-6.x [, ].Cloned Kir channel cDNAs encode proteins of between ~370-500 residues, both N- and C-termini are thought to be cytoplasmic, and the N terminus lacks a signal sequence. Kir channel alpha subunits possess only 2TM domains linked with a P-domain. Thus, Kir channels share similarity with the fifth and sixth domains, and P-domain of the other families. It is thought that four Kir subunits assemble to form a tetrameric channel complex, which may be hetero- or homomeric [].The Kir3.x channel family is gated by G-proteins following G-proteincoupled receptor (GPCR) activation. They are widely distributed inneuronal, atrial, and endocrine tissues and play key roles in generatinglateinhibitory postsynaptic potentials, slowing the heart rate andmodulating hormone release. They are directly activated by G-proteinbeta-gamma subunits released from G-protein heterotrimers of the G(i/o)family upon appropriate receptor stimulation.Kir3.2 is thought to associate with Kir3.1 to form Kir channel heteromersin heart tissue. In central neurones, Kir3.2 homomers may exist, althoughthese may contain combinations of the three splice variants of Kir3.2 thathave been identified []. Weaver mice, which suffer neurological andreproductive deficits, have a point mutation in the gene encoding Kir3.2.This lies in the pore-forming domain of the channel, and as a result theylose their selectivity for K+, allowing Na+ to pass through the channel pore [].
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers []. In eukaryotic cells, K+channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].All K+channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+channels; and three types of calcium (Ca)-activated K+channels (BK, IK and SK) []. The 2TM domain family comprises inward-rectifying K+channels. In addition, there are K+channel alpha-subunits that possess two P-domains. These are usually highly regulated K+selective leak channels.The Kv family can be divided into several subfamilies on the basis of sequence similarity and function. Four of these subfamilies, Kv1 (Shaker), Kv2 (Shab), Kv3 (Shaw) and Kv4 (Shal), consist of pore-forming alpha subunits that associate with different types of beta subunit. Each alpha subunit comprises six hydrophobic TM domains with a P-domain between the fifth and sixth, which partially resides in the membrane. The fourth TM domain has positively charged residues at every third residue and acts as a voltage sensor, which triggers the conformational change that opens the channel pore in response to a displacement in membrane potential []. More recently, 4 new electrically-silent alpha subunits have been cloned: Kv5 (KCNF), Kv6 (KCNG), Kv8 and Kv9 (KCNS). These subunits do not themselves possess any functional activity, but appear to form heteromeric channels with Kv2 subunits, and thus modulate Shab channel activity []. When highly expressed, they inhibit channel activity, but at lower levels show more specific modulatory actions.The first Kv1 sequence (also known as Shaker) was found in Drosophila melanogaster (Fruit fly). Several vertebrate potassium channels with similar amino acid sequences were subsequently found and, together with the D. melanogaster Shaker channel, now constitute the Kv1 family. The family consists of at least 6 genes (Kv1.1, Kv1.2, Kv1.3, Kv1.4, Kv1.5 and Kv1.6) which each play distinct physiological roles. A conserved motif found towards the C terminus of these channels is required for efficient processing and surface expression []. Variations in this motif account for the differences in cell surface expression and localisation between family members. These channels are mostly expressed in the brain, but can also be found in non-excitable cells, such as lymphocytes []. This entry features the tandem inactivation domain found at the N terminus of the Kv1.4 potassium channel. It is composed of two subdomains. Inactivation domain 1 (ID1, residues 1-38) consists of a flexible N terminus anchored at a 5-turn helix, and is thought to work by occluding the ion pathway, as is the case with a classical ball domain. Inactivation domain 2 (ID2, residues 40-50) is a 2.5 turn helix with a high proportion of hydrophobic residues that probably serves to attach ID1 to the cytoplasmic face of the channel. In this way, it can promote rapid access of ID1 to the receptor site in the open channel. ID1 and ID2 function together to bring about fast inactivation of the Kv1.4 channel, which is important for the role of the channel in short-term plasticity [].
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' groupand the rapidly inactivating 'transient' group.These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers []. In eukaryotic cells, K+channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].All K+channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+channels; and three types of calcium (Ca)-activated K+channels (BK, IK and SK) []. The 2TM domain family comprises inward-rectifying K+channels. In addition, there are K+channel alpha-subunits that possess two P-domains. These are usually highly regulated K+selective leak channels.The Kv family can be divided into several subfamilies on the basis of sequence similarity and function. Four of these subfamilies, Kv1 (Shaker), Kv2 (Shab), Kv3 (Shaw) and Kv4 (Shal), consist of pore-forming alpha subunits that associate with different types of beta subunit. Each alpha subunit comprises six hydrophobic TM domains with a P-domain between the fifth and sixth, which partially resides in the membrane. The fourth TM domain has positively charged residues at every third residue and acts as a voltage sensor, which triggers the conformational change that opens the channel pore in response to a displacement in membrane potential []. More recently, 4 new electrically-silent alpha subunits have been cloned: Kv5 (KCNF), Kv6 (KCNG), Kv8 and Kv9 (KCNS). These subunits do not themselves possess any functional activity, but appear to form heteromeric channels with Kv2 subunits, and thus modulate Shab channel activity []. When highly expressed, they inhibit channel activity, but at lower levels show more specific modulatory actions.The first Kv1 sequence (also known as Shaker) was found in Drosophila melanogaster (Fruit fly). Several vertebrate potassium channels with similar amino acid sequences were subsequently found and, together with the D. melanogaster Shaker channel, now constitute the Kv1 family. The family consists of at least 6 genes (Kv1.1, Kv1.2, Kv1.3, Kv1.4, Kv1.5 and Kv1.6) which each play distinct physiological roles. A conserved motif found towards the C terminus of these channels is required for efficient processing and surface expression []. Variations in this motif account for the differences in cell surface expression and localisation between family members. These channels are mostly expressed in the brain, but can also be found in non-excitable cells, such as lymphocytes []. Kv1.4 channels are found in similar regions to Kv1.1 channels. They areparticularly targeted to axons and possibly terminals, suggesting apre-synaptic role in synaptic transmission.
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers []. In eukaryotic cells, K+channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].All K+channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+channels; and three types of calcium (Ca)-activated K+channels (BK, IK and SK) []. The 2TM domain family comprises inward-rectifying K+channels. In addition, there are K+channel alpha-subunits that possess two P-domains. These are usually highly regulated K+selective leak channels.The Kv family can be divided into several subfamilies on the basis of sequence similarity and function. Four of these subfamilies, Kv1 (Shaker), Kv2 (Shab), Kv3 (Shaw) and Kv4 (Shal), consist of pore-forming alpha subunits that associate with different types of beta subunit. Each alpha subunit comprises six hydrophobic TM domains with a P-domain between the fifth and sixth, which partially resides in the membrane. The fourth TM domain has positively charged residues at every third residue and acts as a voltage sensor, which triggers the conformational change that opens the channel pore in response to a displacement in membrane potential []. More recently, 4 new electrically-silent alpha subunits have been cloned: Kv5 (KCNF), Kv6 (KCNG), Kv8 and Kv9 (KCNS). These subunits do not themselves possess any functional activity, but appear to form heteromeric channels with Kv2 subunits, and thus modulate Shab channel activity []. When highly expressed, they inhibit channel activity, but at lower levels show more specific modulatory actions.A voltage-dependent potassium channel gene designated Shaw was initially isolated from Drosophila melanogaster (Fruit fly). Subsequently, several vetebrate potassium channels with similar amino acid sequences were found and, together with the D. melanogaster channel, now constitute the Kv3 family. These channels are thought to play a role in shortening of action potential durations and modulating pre-synaptic neurotransmitter release. In mammals, the family consists of 4 genes (Kv3.1, Kv3.2, Kv3.3 and Kv3.4). Each gene product has its own subcellular location and function.Kv3.3 channels are evenly distributed over the soma and proximal apical dendrites. They have also been found in the lens epithelium, corneal endothelium, cerebellar cells and the deep cerebellar nuclei. When co-expressed with NADPH oxidase, they function as an oxygen sensor complex in airway chemoreceptors.
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers []. In eukaryotic cells, K+channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].All K+channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+channels; and three types of calcium (Ca)-activated K+channels (BK, IK and SK) []. The 2TM domain family comprises inward-rectifying K+channels. In addition, there are K+channel alpha-subunits that possess two P-domains. These are usually highly regulated K+selective leak channels.The Kv family can be divided into several subfamilies on the basis of sequence similarity and function. Four of these subfamilies, Kv1 (Shaker), Kv2 (Shab), Kv3 (Shaw) and Kv4 (Shal), consist of pore-forming alpha subunits that associate with different types of beta subunit. Each alpha subunit comprises six hydrophobic TM domains with a P-domain between the fifth and sixth, which partially resides in the membrane. The fourth TM domain has positively charged residues at every third residue and acts as a voltage sensor, which triggers the conformational change that opens the channel pore in response to a displacement in membrane potential []. More recently, 4 new electrically-silent alpha subunits have been cloned: Kv5 (KCNF), Kv6 (KCNG), Kv8 and Kv9 (KCNS). These subunits do not themselves possess any functional activity, but appear to form heteromeric channels with Kv2 subunits, and thus modulate Shab channel activity []. When highly expressed, they inhibit channel activity, but at lower levels show more specific modulatory actions.A voltage-dependent potassium channel gene designated Shaw was initially isolated from Drosophila melanogaster (Fruit fly). Subsequently, several vetebrate potassium channels with similar amino acid sequences were found and, together with the D. melanogaster channel, now constitute the Kv3 family. These channels are thought to play a role in shortening of action potential durations and modulating pre-synaptic neurotransmitter release. In mammals, the family consists of 4 genes (Kv3.1, Kv3.2, Kv3.3 and Kv3.4). Each gene product has its own subcellular location and function.Kv3.4 channels are expressed in cells that surround the cerebellar Purkinje cells. In the presence of protein kinase C, rapid inactivation is eliminated, resulting in a non-inactivating delayed rectifying current. The implications of this are seen for signal encoding in the central nervous system.
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers []. In eukaryotic cells, K+channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].All K+channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+channels; and three types of calcium (Ca)-activated K+channels (BK, IK and SK) []. The 2TM domain family comprises inward-rectifying K+channels. In addition, there are K+channel alpha-subunits that possess two P-domains. These are usually highly regulated K+selective leak channels.The Kv family can be divided into several subfamilies on the basis of sequence similarity and function. Four of these subfamilies, Kv1 (Shaker), Kv2 (Shab), Kv3 (Shaw) and Kv4 (Shal), consist of pore-forming alpha subunits that associate with different types of beta subunit. Each alpha subunit comprises six hydrophobic TM domains with a P-domain between the fifth and sixth, which partially resides in the membrane. The fourth TM domain has positively charged residues at every third residue and acts as a voltage sensor, which triggers the conformational change that opens the channel pore in response to a displacement in membrane potential []. More recently, 4 new electrically-silent alpha subunits have been cloned: Kv5 (KCNF), Kv6 (KCNG), Kv8 and Kv9 (KCNS). These subunits do not themselves possess any functional activity, but appear to form heteromeric channels with Kv2 subunits, and thus modulate Shab channel activity []. When highly expressed, they inhibit channel activity, but at lower levels show more specific modulatory actions.A voltage-dependent potassium channel gene designated Shaw was initially isolated from Drosophila melanogaster (Fruit fly). Subsequently, several vetebrate potassium channels with similar amino acid sequences were found and, together with the D. melanogaster channel, now constitute the Kv3 family. These channels are thought to play a role in shortening of action potential durations and modulating pre-synaptic neurotransmitter release. In mammals, the family consists of 4 genes (Kv3.1, Kv3.2, Kv3.3 and Kv3.4). Each gene product has its own subcellular location and function.Kv3.1 channels have slow-rising delayed rectifier-type outward currents that inactivate slowly. They have a tentative role in the fast action potential repolarisation abundant in rapidly firing neurons, such as the auditory brainstem, and hippocampal and cortical interneurons. There are two forms, -a and -b, which differ in expression during development. Kv3.1a appears to be found in the neurons of the adult brain, whereas Kv3.1b is expressed in embryonic and perinatal neurons. In addition, Kv3.1 channels can also be found in T-lymphocytes.
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers []. In eukaryotic cells, K+channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].All K+channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+channels; and three types of calcium (Ca)-activated K+channels (BK, IK and SK) []. The 2TM domain family comprises inward-rectifying K+channels. In addition, there are K+channel alpha-subunits that possess two P-domains. These are usually highly regulated K+selective leak channels.2P-domain channels influence the resting membrane potential and as a result can control cell excitability. In addition, they pass K+in response to changes in membrane potential, and are also tightly regulated by molecular oxygen, GABA (gamma-aminobutyric acid), noradrenaline and serotonin.The first member of this family (TOK1), cloned from Saccharomyces cerevisiae [], ispredicted to have eight potential transmembrane (TM) helices. However,subsequently-cloned two P-domain family members from Drosophila andmammalian species are predicted to have only four TM segments. They areusually referred to as TWIK-related channels (Tandem of P-domains in a Weakly Inward rectifying K+ channel) [, , , ]. Functional characterisation of these channels has revealed a diversity of properties in that they may show inward or outward rectification, their activity may be modulated in different directions by protein phosphorylation, and their sensitivity to changes in intracellular or extracellular pH varies. Despite these disparate properties, they are all thought to share the same topology offour TM segments, including two P-domains. That TWIK-related K+ channelsall produce instantaneous and non-inactivating K+ currents, which do notdisplay a voltage-dependent activation threshold, suggests that they arebackground (leak) K+ channels involved in the generation and modulation of the resting membrane potential in various cell types. Further studies have revealed that they may be found in many species, including: plants, invertebrates and mammals.TWIK family members (TWIK-1 and TWIK-2) produce constitutive K+ currents of weak amplitude []. They are present in a variety of tissues, including brain and cells of the immune system. Together with their functional properties, theirwide distribution suggests that these channels may be involved in the control of background K+ conductances in many cell types.TWIK-1 was the first two P-domain K+channel subunit cloned from humantissue []. It is widely distributed, being particularly abundant in thebrain and heart. It forms a weak inward rectifer K+channel, and has beenfound to be inhibited by internal acidification; its activity is enhancedby protein kinase C phosphorylation.
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other secondmessengers []. In eukaryotic cells, K+channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].All K+channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+channels; and three types of calcium (Ca)-activated K+channels (BK, IK and SK) []. The 2TM domain family comprises inward-rectifying K+channels. In addition, there are K+channel alpha-subunits that possess two P-domains. These are usually highly regulated K+selective leak channels.2P-domain channels influence the resting membrane potential and as a result can control cell excitability. In addition, they pass K+in response to changes in membrane potential, and are also tightly regulated by molecular oxygen, GABA (gamma-aminobutyric acid), noradrenaline and serotonin.The first member of this family (TOK1), cloned from Saccharomyces cerevisiae [], ispredicted to have eight potential transmembrane (TM) helices. However,subsequently-cloned two P-domain family members from Drosophila andmammalian species are predicted to have only four TM segments. They areusually referred to as TWIK-related channels (Tandem of P-domains in a Weakly Inward rectifying K+ channel) [, , , ]. Functional characterisation of these channels has revealed a diversity of properties in that they may show inward or outward rectification, their activity may be modulated in different directions by protein phosphorylation, and their sensitivity to changes in intracellular or extracellular pH varies. Despite these disparate properties, they are all thought to share the same topology offour TM segments, including two P-domains. That TWIK-related K+ channelsall produce instantaneous and non-inactivating K+ currents, which do notdisplay a voltage-dependent activation threshold, suggests that they arebackground (leak) K+ channels involved in the generation and modulation of the resting membrane potential in various cell types. Further studies have revealed that they may be found in many species, including: plants, invertebrates and mammals.TWIK family members (TWIK-1 and TWIK-2) produce constitutive K+ currents of weak amplitude []. They are present in a variety of tissues, including brain and cells of the immune system. Together with their functional properties, their wide distribution suggests that these channels may be involved in the control of background K+ conductances in many cell types.TWIK-2 is expressed in the gastrointestinal tract, as well as the brain and immune system. The transient and delayed activities of TWIK-2 suggeststhat it may play an important role in cell electrogenesis [, ]. Pharmacologically, TWIK-2 channels are distinct from TWIK-1 channels in terms of their response to quinidine and barium. They are inhibited by intracellular, but not extracellular, acidification [].
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers []. In eukaryotic cells, K+channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].All K+channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+channels; and three types of calcium (Ca)-activated K+channels (BK, IK and SK) []. The 2TM domain family comprises inward-rectifying K+channels. In addition, there are K+channel alpha-subunits that possess two P-domains. These are usually highly regulated K+selective leak channels.The Kv family can be divided into several subfamilies on the basis of sequence similarity and function. Four of these subfamilies, Kv1 (Shaker), Kv2 (Shab), Kv3 (Shaw) and Kv4 (Shal), consist of pore-forming alpha subunits that associate with different types of beta subunit. Each alpha subunit comprises six hydrophobic TM domains with a P-domain between the fifth and sixth, which partially resides in the membrane. The fourth TM domain has positively charged residues at every third residue and acts as a voltage sensor, which triggers the conformational change that opens the channel pore in response to a displacement in membrane potential []. More recently, 4 new electrically-silent alpha subunits have been cloned: Kv5 (KCNF), Kv6 (KCNG), Kv8 and Kv9 (KCNS). These subunits do not themselves possess any functional activity, but appear to form heteromeric channels with Kv2 subunits, and thus modulate Shab channel activity []. When highly expressed, they inhibit channel activity, but at lower levels show more specific modulatory actions.The Kv2 voltage-dependent potassium channels (also known as the Shab family) are responsible for much of the delayed rectifier current in Drosophila melanogaster (Fruit fly) nervous system and muscle. However, in vertebrates, Kv2 channels have been shwon to be involved in the delayed rectifier currents of the heart and skeletal muscles. They are also thought to be important in determining intrinsic neuronal excitability in both mammals and non-mammals []. Kv2 channels can be further divided into 2 subtypes, designated Kv2.1 and Kv2.2.The first Kv2.2 channel was cloned from rat and was originally referred to as the circumvillate papilla delayed rectifying K+channel or cDRK. Several mammalian channels have subsequently been found and, together with the rat Kv2.2 channel, form a small subfamily. They are predominantly expressed in the interneurones; however, their roles are largely undetermined.
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers []. In eukaryotic cells, K+channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].All K+channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+channels; and three types of calcium (Ca)-activated K+channels (BK, IK and SK) []. The 2TM domain family comprises inward-rectifying K+channels. In addition, there are K+channel alpha-subunits that possess two P-domains. These are usually highly regulated K+selective leak channels.2P-domain channels influence the resting membrane potential and as a result can control cell excitability. In addition, they pass K+in response to changes in membrane potential, and are also tightly regulated by molecular oxygen, GABA (gamma-aminobutyric acid), noradrenaline and serotonin.The first member of this family (TOK1), cloned from Saccharomyces cerevisiae [], ispredicted to have eight potential transmembrane (TM) helices. However,subsequently-cloned two P-domain family members from Drosophila andmammalian species are predicted to have only four TM segments. They areusually referred to as TWIK-related channels (Tandem of P-domains in a Weakly Inward rectifying K+ channel) [, , , ]. Functional characterisation of these channels has revealed a diversity of properties in that they may show inward or outward rectification, their activity may be modulated in different directions by protein phosphorylation, and their sensitivity to changes in intracellular or extracellular pH varies. Despite these disparate properties, they are all thought to share the same topology offour TM segments, including two P-domains. That TWIK-related K+ channelsall produce instantaneous and non-inactivating K+ currents, which do notdisplay a voltage-dependent activation threshold, suggests that they arebackground (leak) K+ channels involved in the generation and modulation of the resting membrane potential in various cell types. Further studies have revealed that they may be found in many species, including: plants, invertebrates and mammals.TREK is a member of the TWIK-related (2-pore domain) K+ channel familyidentifed in human tissues. It has two members, designated TREK-1 and TREK-2. TREK-1 is distributed in neuronal, cardiac and smooth muscle cells, whereasTREK-2 has been shown to be expressed in the cerebellum [, ]. Both membersare known as mechano-sensitive and unsaturated fatty acid-activated K+channels as they are opened by membrane stretch, cell swelling, shearstress and polyunsaturated fatty acids, such as arachidonic acid [].
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers []. In eukaryotic cells, K+channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].All K+channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain containsthe sequence (T/SxxTxGxG), which has been termed the K+selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+channels; and three types of calcium (Ca)-activated K+channels (BK, IK and SK) []. The 2TM domain family comprises inward-rectifying K+channels. In addition, there are K+channel alpha-subunits that possess two P-domains. These are usually highly regulated K+selective leak channels.2P-domain channels influence the resting membrane potential and as a result can control cell excitability. In addition, they pass K+in response to changes in membrane potential, and are also tightly regulated by molecular oxygen, GABA (gamma-aminobutyric acid), noradrenaline and serotonin.The first member of this family (TOK1), cloned from Saccharomyces cerevisiae [], ispredicted to have eight potential transmembrane (TM) helices. However,subsequently-cloned two P-domain family members from Drosophila andmammalian species are predicted to have only four TM segments. They areusually referred to as TWIK-related channels (Tandem of P-domains in a Weakly Inward rectifying K+ channel) [, , , ]. Functional characterisation of these channels has revealed a diversity of properties in that they may show inward or outward rectification, their activity may be modulated in different directions by protein phosphorylation, and their sensitivity to changes in intracellular or extracellular pH varies. Despite these disparate properties, they are all thought to share the same topology offour TM segments, including two P-domains. That TWIK-related K+ channelsall produce instantaneous and non-inactivating K+ currents, which do notdisplay a voltage-dependent activation threshold, suggests that they arebackground (leak) K+ channels involved in the generation and modulation of the resting membrane potential in various cell types. Further studies have revealed that they may be found in many species, including: plants, invertebrates and mammals.TRAAK (TWIK-related arachidonic acid-stimulated K+ channel) is a member ofthe 2P-domain K+ channel family, and is expressed mainly in the brain andplacenta. It is strongly activated by unsaturated fatty acids, such asoleate and linoleate. An alternative way of activating TRAAK channels is theapplication of stretch to the cell membrane, for example, by means of cellswelling, shear stress or negative pressure [].
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers []. In eukaryotic cells, K+channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].All K+channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+channels; and three types of calcium (Ca)-activated K+channels (BK, IK and SK) []. The 2TM domain family comprises inward-rectifying K+channels. In addition, there are K+channel alpha-subunits that possess two P-domains. These are usually highly regulated K+selective leak channels.The Kv family can be divided into several subfamilies on the basis of sequence similarity and function. Four of these subfamilies, Kv1 (Shaker), Kv2 (Shab), Kv3 (Shaw) and Kv4 (Shal), consist of pore-forming alpha subunits that associate with different types of beta subunit. Each alpha subunit comprises six hydrophobic TM domains with a P-domain between the fifth and sixth, which partially resides in the membrane. The fourth TM domain has positively charged residues at every third residue and acts as a voltage sensor, which triggers the conformational change that opens the channel pore in response to a displacement in membrane potential []. More recently, 4 new electrically-silent alpha subunits have been cloned: Kv5 (KCNF), Kv6 (KCNG), Kv8 and Kv9 (KCNS). These subunits do not themselves possess any functional activity, but appear to form heteromeric channels with Kv2 subunits, and thus modulate Shab channel activity []. When highly expressed, they inhibit channel activity, but at lower levels show more specific modulatory actions.The first Kv1 sequence (also known as Shaker) was found in Drosophila melanogaster (Fruit fly). Several vertebrate potassium channels with similar amino acid sequences were subsequently found and, together with the D. melanogaster Shaker channel, now constitute the Kv1 family. The family consists of at least 6 genes (Kv1.1, Kv1.2, Kv1.3, Kv1.4, Kv1.5 and Kv1.6) which each play distinct physiological roles. A conserved motif found towards the C terminus of these channels is required for efficient processing and surface expression []. Variations in this motif account for the differences in cell surface expression and localisation between family members. These channels are mostly expressed in the brain, but can also be found in non-excitable cells, such as lymphocytes []. This entry features the tandem inactivation domain superfamily found at the N terminus of the Kv1.4 potassium channel. It is composed of two subdomains. Inactivation domain 1 (ID1, residues 1-38) consists of a flexible N terminus anchored at a 5-turn helix, and is thought to work by occluding the ion pathway, as is the case with a classical ball domain. Inactivation domain 2 (ID2, residues 40-50) is a 2.5 turn helix with a high proportion of hydrophobic residues that probably serves to attach ID1 to the cytoplasmic face of the channel. In this way, it can promote rapid access of ID1 to the receptor site in the open channel. ID1 and ID2 function together to bring about fast inactivation of the Kv1.4 channel, which is important for the role of the channel in short-term plasticity [].
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers []. In eukaryotic cells, K+channels are involved in neural signalling and generation of the cardiac rhythm, act as effectorsin signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].All K+channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+channels; and three types of calcium (Ca)-activated K+channels (BK, IK and SK) []. The 2TM domain family comprises inward-rectifying K+channels. In addition, there are K+channel alpha-subunits that possess two P-domains. These are usually highly regulated K+selective leak channels.The Kv family can be divided into several subfamilies on the basis of sequence similarity and function. Four of these subfamilies, Kv1 (Shaker), Kv2 (Shab), Kv3 (Shaw) and Kv4 (Shal), consist of pore-forming alpha subunits that associate with different types of beta subunit. Each alpha subunit comprises six hydrophobic TM domains with a P-domain between the fifth and sixth, which partially resides in the membrane. The fourth TM domain has positively charged residues at every third residue and acts as a voltage sensor, which triggers the conformational change that opens the channel pore in response to a displacement in membrane potential []. More recently, 4 new electrically-silent alpha subunits have been cloned: Kv5 (KCNF), Kv6 (KCNG), Kv8 and Kv9 (KCNS). These subunits do not themselves possess any functional activity, but appear to form heteromeric channels with Kv2 subunits, and thus modulate Shab channel activity []. When highly expressed, they inhibit channel activity, but at lower levels show more specific modulatory actions.A voltage-dependent potassium channel gene designated Shaw was initially isolated from Drosophila melanogaster (Fruit fly). Subsequently, several vetebrate potassium channels with similar amino acid sequences were found and, together with the D. melanogaster channel, now constitute the Kv3 family. These channels are thought to play a role in shortening of action potential durations and modulating pre-synaptic neurotransmitter release. In mammals, the family consists of 4 genes (Kv3.1, Kv3.2, Kv3.3 and Kv3.4). Each gene product has its own subcellular location and function.This particular family model is based on Kv3x proteins from invertebrates, such as Caenorhabditis elegans, Drosophila melanogaster (Fruit fly), Anopheles gambiae (African malaria mosquito), and Aplysia californica (California sea hare).
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers []. In eukaryotic cells, K+channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].All K+channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+channels; and three types of calcium (Ca)-activated K+channels (BK, IK and SK) []. The 2TM domain family comprises inward-rectifying K+channels. In addition, there are K+channel alpha-subunits that possess two P-domains. These are usually highly regulated K+selective leak channels.The Kv family can be divided into several subfamilies on the basis of sequence similarity and function. Four of these subfamilies, Kv1 (Shaker), Kv2 (Shab), Kv3 (Shaw) and Kv4 (Shal), consist of pore-forming alpha subunits that associate with different types of beta subunit. Each alpha subunit comprises six hydrophobic TM domains with a P-domain between the fifth and sixth, which partially resides in the membrane. The fourth TM domain has positively charged residues at every third residue and acts as a voltage sensor, which triggers the conformational change that opens the channel pore in response to a displacement in membrane potential []. More recently, 4 new electrically-silent alpha subunits have been cloned: Kv5 (KCNF), Kv6 (KCNG), Kv8 and Kv9 (KCNS). These subunits do not themselves possess any functional activity, but appear to form heteromeric channels with Kv2 subunits, and thus modulate Shab channel activity []. When highly expressed, they inhibit channel activity, but at lower levels show more specific modulatory actions.A voltage-dependent potassium channel gene designated Shaw was initially isolated from Drosophila melanogaster (Fruit fly). Subsequently, several vetebrate potassium channels with similar amino acid sequences were found and, together with the D. melanogaster channel, now constitute the Kv3 family. These channels are thought to play a role in shortening of action potential durations and modulating pre-synaptic neurotransmitter release. In mammals, the family consists of 4 genes (Kv3.1, Kv3.2, Kv3.3 and Kv3.4). Each gene product has its own subcellular location and function.Fast inactivation of voltage-dependent potassium channels controls membrane excitability and signal propagation in central neurons. This occurs by a 'ball-and-chain'-type mechanism where an N-terminal protein inactivation domain occludes the pore from the cytoplasmic side. In Kv3 channels this process is regulated by protein phosphorylation, where phosphorylation of serine residues leads to a reduction or removal of the fast inactivation [].
