| First Author | Sun X | Year | 2013 |
| Journal | J Neurosci | Volume | 33 |
| Issue | 27 | Pages | 11253-61 |
| PubMed ID | 23825428 | Mgi Jnum | J:199823 |
| Mgi Id | MGI:5505351 | Doi | 10.1523/JNEUROSCI.0620-13.2013 |
| Citation | Sun X, et al. (2013) The interface between membrane-spanning and cytosolic domains in Ca(2)(+)-dependent K(+) channels is involved in beta subunit modulation of gating. J Neurosci 33(27):11253-61 |
| abstractText | Large-conductance, voltage-, and Ca(2)(+)-dependent K(+) (BK) channels are broadly expressed in various tissues to modulate neuronal activity, smooth muscle contraction, and secretion. BK channel activation depends on the interactions among the voltage sensing domain (VSD), the cytosolic domain (CTD), and the pore gate domain (PGD) of the Slo1 alpha-subunit, and is further regulated by accessory beta subunits (beta1-beta4). How beta subunits fine-tune BK channel activation is critical to understand the tissue-specific functions of BK channels. Multiple sites in both Slo1 and the beta subunits have been identified to contribute to the interaction between Slo1 and the beta subunits. However, it is unclear whether and how the interdomain interactions among the VSD, CTD, and PGD are altered by the beta subunits to affect channel activation. Here we show that human beta1 and beta2 subunits alter interactions between bound Mg(2)(+) and gating charge R213 and disrupt the disulfide bond formation at the VSD-CTD interface of mouse Slo1, indicating that the beta subunits alter the VSD-CTD interface. Reciprocally, mutations in the Slo1 that alter the VSD-CTD interaction can specifically change the effects of the beta1 subunit on the Ca(2)(+) activation and of the beta2 subunit on the voltage activation. Together, our data suggest a novel mechanism by which the beta subunits modulated BK channel activation such that a beta subunit may interact with the VSD or the CTD and alter the VSD-CTD interface of the Slo1, which enables the beta subunit to have effects broadly on both voltage and Ca(2)(+)-dependent activation. |
