This entry represents HCN1, which belongs to the hyperpolarisation-activated cyclic nucleotide-gated (HCN) channel family. HCN1 is expressed in the brain, spinal cord, dorsal root ganglion and heart muscle []. It contributes to the native pacemaker currents in heart and in neurons [, , ]. It may be involved in motor learning and hippocampal-dependent network oscillation in mice [, ]. It binds to filaminA, a putative cytoplasmic scaffold protein that binds actin and links transmembrane proteins, such as the K+ channels Kv4.2 and Kir2.1, to the actin cytoskeleton [, , ].The hyperpolarisation-activated cation current (termed I(f), I(h), or I(q)) plays a key role in the initiation and modulation of cardiac and neuronal pacemaker depolarisations. This current is carried by both K+ and Na+ through I(h) or I(f) channels, such as members of the hyperpolarisation-activated cyclic nucleotide-gated (HCN) family. HCN channels belong to the superfamilyof voltage-gated pore loop channels. The voltage-dependent opening ofthe HCN channels is directly regulated by the binding ofcAMP. In vertebrates, the HCN channel family comprises four members (HCN1-4) []. Whereas HCN3 seems to be specifically expressed in neurons, the other three channels (HCN1, 2, and 4) have been detected in both heart and brain [, ]. HCN channels contain six membrane-spanning helices (S1-S6), including a positively charged voltage-sensing S4 segment and an ion-conducting pore between S5 and S6. In the C terminus the channels carry a cyclic nucleotide-binding domain (CNBD) []. Binding of cAMP to the CNBD speeds up channel opening and shifts the voltage-dependence of activation to more positive voltages []. HCN channels exhibit weak selectivity for potassium over sodium ions.
