KCNE1 alters the voltage sensor movements necessary to open the KCNQ1 channel gate
KCNE1 alters the voltage sensor movements necessary to open the KCNQ1 channel gate
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DOI：
10.1073/pnas.1016300108
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发表时间：
2010-12-28
影响因子：
11.1
通讯作者：
Kass, Robert S.
中科院分区：
文献类型：
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作者：
Osteen, Jeremiah D.;Gonzalez, Carlos;Kass, Robert S.
延迟整流I-Ks钾通道由α-（KCNQ 1）和β-（KCNE 1）亚基共组装而成，对心脏功能至关重要。尽管KCNE 1是复制天然I-Ks通道功能特性所必需的，但KCNE 1调节KCNQ 1的机制尚不清楚。在这里，我们报告的测量电压传感器运动KCNQ 1和KCNQ 1/KCNE 1通道使用电压钳荧光法。KCNQ 1通道对荧光和电流信号表现出难以区分的电压依赖性，表明电压传感器移动和通道开放之间存在一对一的关系。KCNE 1共表达显著分离了KCNQ 1/KCNE 1电流和荧光的电压依赖性，这表明在KCNQ 1/KCNE 1通道开放之前需要多个电压传感器的运动。这项工作提供了深入了解KCNE 1调节I-Ks通道的机制，并提出了不同的β亚基调节离子通道蛋白的机制。
The delayed rectifier I-Ks potassium channel, formed by coassembly of alpha-(KCNQ1) and beta-(KCNE1) subunits, is essential for cardiac function. Although KCNE1 is necessary to reproduce the functional properties of the native I-Ks channel, the mechanism(s) through which KCNE1 modulates KCNQ1 is unknown. Here we report measurements of voltage sensor movements in KCNQ1 and KCNQ1/KCNE1 channels using voltage clamp fluorometry. KCNQ1 channels exhibit indistinguishable voltage dependence of fluorescence and current signals, suggesting a one-to-one relationship between voltage sensor movement and channel opening. KCNE1 coexpression dramatically separates the voltage dependence of KCNQ1/KCNE1 current and fluorescence, suggesting an imposed requirement for movements of multiple voltage sensors before KCNQ1/KCNE1 channel opening. This work provides insight into the mechanism by which KCNE1 modulates the I-Ks channel and presents a mechanism for distinct beta-subunit regulation of ion channel proteins.