The interface between membrane-spanning and cytosolic domains in Ca2+-dependent K+ channels is involved in β subunit modulation of gating

Xiaohui Sun, Jingyi Shi, Kelli Delaloye, Xiao Yang, Huanghe Yang, Guohui Zhang, Jianmin Cui

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Large-conductance, voltage-, and Ca2+-dependent K+ (BK) channels are broadly expressed in various tissues to modulate neuronal activity, smooth muscle contraction, and secretion.BKchannel activation depends on the interactions among the voltage sensing domain (VSD), the cytosolic domain (CTD), and the pore gate domain (PGD) of the Slo1 α-subunit, and is further regulated by accessory β subunits (β1-β4). Howβ subunits fine-tune BK channel activation is critical to understand the tissue-specific functions of BK channels. Multiple sites in both Slo1 and the β subunits have been identified to contribute to the interaction between Slo1 and the β subunits. However, it is unclear whether andhowthe interdomain interactionsamongthe VSD, CTD, andPGDare altered by theβ subunits to affect channel activation. Here we show that human β1 and β2 subunits alter interactions between bound Mg2+ and gating charge R213 and disrupt the disulfide bond formation at theVSD-CTDinterface ofmouseSlo1, indicating that theβ subunits alter theVSD-CTDinterface. Reciprocally, mutations in the Slo1 that alter the VSD-CTD interaction can specifically change the effects of theβ1 subunit on the Ca2+ activation and of the β2 subunit on the voltage activation. Together, our data suggest a novel mechanism by which the β subunits modulatedBKchannel activation such that aβ subunitmayinteract with theVSDor theCTDand alter theVSD-CTDinterface of the Slo1, which enables the β subunit to have effects broadly on both voltage and Ca2+-dependent activation.

Original languageEnglish
Pages (from-to)11253-11261
Number of pages9
JournalJournal of Neuroscience
Volume33
Issue number27
DOIs
StatePublished - 2013

Fingerprint

Dive into the research topics of 'The interface between membrane-spanning and cytosolic domains in Ca2+-dependent K+ channels is involved in β subunit modulation of gating'. Together they form a unique fingerprint.

Cite this