TY - JOUR
T1 - The interface between membrane-spanning and cytosolic domains in Ca2+-dependent K+ channels is involved in β subunit modulation of gating
AU - Sun, Xiaohui
AU - Shi, Jingyi
AU - Delaloye, Kelli
AU - Yang, Xiao
AU - Yang, Huanghe
AU - Zhang, Guohui
AU - Cui, Jianmin
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84880503009&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.0620-13.2013
DO - 10.1523/JNEUROSCI.0620-13.2013
M3 - Article
C2 - 23825428
AN - SCOPUS:84880503009
SN - 0270-6474
VL - 33
SP - 11253
EP - 11261
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 27
ER -