Inactivation of KCNQ1 potassium channels reveals dynamic coupling between voltage sensing and pore opening.
Inactivation of KCNQ1 potassium channels reveals dynamic coupling between voltage sensing and pore opening.
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DOI：
10.1038/s41467-017-01911-8
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发表时间：
2017-11-23
影响因子：
16.6
通讯作者：
Cui J
中科院分区：
文献类型：
--
作者：
Hou P;Eldstrom J;Shi J;Zhong L;McFarland K;Gao Y;Fedida D;Cui J
在电压激活的离子通道中，电压传感器(VSD)的激活通过VSD-孔耦合来诱导孔的打开。以往的研究表明，当VSD激活到中间和完全激活状态时，KCNQ1通道中的孔洞打开，分别导致中间打开(IO)和激活打开(AO)状态。众所周知，伴随着KCNQ1通道的开放，离子电流被称为失活的快速过程所抑制。在这里，我们证明了KCNQ1通道的失活源于VSD-孔道耦合的不同机制，这些机制分别导致IO和AO状态。当VSD从中间状态激活到激活状态时，VSD-孔耦合在打开孔方面的效果较差，从而产生失活。这些结果表明，在电压依赖的离子通道激活中，除了典型的VSD-孔道耦合之外，还有不同的机制在起作用。KCNQ1是一种电压门控性钾通道，在心脏和上皮功能中起重要作用。在这里，作者提出了一种KCNQ1激活和失活的机制，其中电压传感器激活在中间打开状态下比完全打开状态下更有效地促进孔的打开，从而产生失活。
In voltage-activated ion channels, voltage sensor (VSD) activation induces pore opening via VSD-pore coupling. Previous studies show that the pore in KCNQ1 channels opens when the VSD activates to both intermediate and fully activated states, resulting in the intermediate open (IO) and activated open (AO) states, respectively. It is also well known that accompanying KCNQ1 channel opening, the ionic current is suppressed by a rapid process called inactivation. Here we show that inactivation of KCNQ1 channels derives from the different mechanisms of the VSD-pore coupling that lead to the IO and AO states, respectively. When the VSD activates from the intermediate state to the activated state, the VSD-pore coupling has less efficacy in opening the pore, producing inactivation. These results indicate that different mechanisms, other than the canonical VSD-pore coupling, are at work in voltage-dependent ion channel activation. KCNQ1 is a voltage-gated potassium channel that is important in cardiac and epithelial function. Here the authors present a mechanism for KCNQ1 activation and inactivation in which voltage sensor activation promotes pore opening more effectively in the intermediate open state than the fully open state, generating inactivation.
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电压传感器和孔之间需要两个独立的接口来实现电压依赖性 K(+) 通道的功能。
影响因子：
9.8
作者：
Lee, Seok-Yong;Banerjee, Anirban;MacKinnon, Roderick
通讯作者：
MacKinnon, Roderick
DOI：
10.1085/jgp.201210840
发表时间：
2012-12
期刊：
The Journal of general physiology
影响因子：
--
作者：
Chowdhury S;Chanda B
通讯作者：
Chanda B
影响因子：
3.8
作者：
Ledwell, JL;Aldrich, RW
通讯作者：
Aldrich, RW
影响因子：
16.2
作者：
Larsson, HP;Baker, OS;Isacoff, EY
通讯作者：
Isacoff, EY
影响因子：
3.4
作者：
Gibor, Gilad;Yakubovich, Daniel;Attali, Bernard
通讯作者：
Attali, Bernard