| First Author | Morrow JP | Year | 2006 |
| Journal | Proc Natl Acad Sci U S A | Volume | 103 |
| Issue | 13 | Pages | 5096-101 |
| PubMed ID | 16549765 | Mgi Jnum | J:248287 |
| Mgi Id | MGI:6093438 | Doi | 10.1073/pnas.0600907103 |
| Citation | Morrow JP, et al. (2006) Defining the BK channel domains required for beta1-subunit modulation. Proc Natl Acad Sci U S A 103(13):5096-101 |
| abstractText | In a wide variety of cell types, including neurons and smooth muscle cells, activation of the large-conductance voltage- and Ca(2+)-activated K(+) (BK) channels causes transient membrane hyperpolarization, thereby regulating cellular excitability. Similar to other voltage-gated ion channels, BK channels, a tetramer of alpha-subunits, associate with auxiliary beta-subunits in a tissue-specific manner, modifying the channel's gating properties. The BK beta1-subunit, which is expressed in smooth muscle, increases the apparent Ca(2+) sensitivity (marked by a hyperpolarizing shift in the conductance-voltage relationship at a given Ca(2+) concentration), slows macroscopic activation and deactivation, and is required for channel activation by 17beta-estradiol. The beta1-subunit is essential for normal regulation of vascular smooth muscle contractility and blood pressure. Little is known, however, about the molecular mechanisms of beta1-subunit modulation of alpha-subunits. Here we show that the beta1-subunit's modulation of the Ca(2+) and 17beta-estradiol sensitivities can be dissociated from its effects on gating kinetics by truncation of the alpha-subunit's extracellular N-terminal residues. The BK alpha-subunit N terminus interacts uniquely with the beta1-subunit: beta2 regulation of the alpha-subunit is unaltered by truncation of the N terminus. Although the functional interaction of alpha and beta1 requires the N-terminal tail of alpha, the physical association requires the S1, S2, and S3 transmembrane helices of alpha. |
