Voltage-Dependent Gating: Novel Insights from KCNQ1 Channels
Voltage-Dependent Gating: Novel Insights from KCNQ1 Channels
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DOI：
10.1016/j.bpj.2015.11.023
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发表时间：
2016-01-05
影响因子：
3.4
通讯作者：
Cui, Jianmin
中科院分区：
文献类型：
--
作者：
Cui, Jianmin
电压依赖性阳离子通道的门控涉及三个一般的分子过程：电压传感器激活、传感器-孔耦合和孔开放。KCNQ1是一种电压门控钾(Kv)通道，其独特的特性为电压依赖门控的基本原理提供了新的见解。1)与其他Kv通道类似，KCNQ1电压传感器的激活经历了两个可分解的步骤；但是，KCNQ1所特有的是，孔在电压传感器激活的中间和激活状态下都打开。在中间开放和激活开放两种状态下，电压传感器-孔的耦合不同，导致在电压传感器激活过程中开放孔的性质发生变化。2)电压传感器-孔道耦合和孔道开放分别需要膜脂PIP2和细胞内ATP作为辅因子，因此电压依赖的门控依赖于多种刺激，包括细胞内信号分子的结合。这些机制是KCNQ1通道特殊的KCNE1亚基修饰的基础，并具有重要的生理意义。
Gating of voltage-dependent cation channels involves three general molecular processes: voltage sensor activation, sensor-pore coupling, and pore opening. KCNQ1 is a voltage-gated potassium (Kv) channel whose distinctive properties have provided novel insights on fundamental principles of voltage-dependent gating. 1) Similar to other Kv channels, KCNQ1 voltage sensor activation undergoes two resolvable steps; but, unique to KCNQ1, the pore opens at both the intermediate and activated state of voltage sensor activation. The voltage sensor-pore coupling differs in the intermediate-open and the activated-open states, resulting in changes of open pore properties during voltage sensor activation. 2) The voltage sensor-pore coupling and pore opening require the membrane lipid PIP2 and intracellular ATP, respectively, as cofactors, thus voltage-dependent gating is dependent on multiple stimuli, including the binding of intracellular signaling molecules. These mechanisms underlie the extraordinary KCNE1 subunit modification of the KCNQ1 channel and have significant physiological implications.