文章基本信息

标题：Modulation of voltage-gated K+ channels by the sodium channel β1 subunit
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作者：Hai M. Nguyen ; Haruko Miyazaki ; Naoto Hoshi 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2012
卷号：109
期号：45
页码：18577-18582
DOI：10.1073/pnas.1209142109
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Voltage-gated sodium (NaV) and potassium (KV) channels are critical components of neuronal action potential generation and propagation. Here, we report that NaV{beta}1 encoded by SCN1b, an integral subunit of NaV channels, coassembles with and modulates the biophysical properties of KV1 and KV7 channels, but not KV3 channels, in an isoform-specific manner. Distinct domains of NaV{beta}1 are involved in modulation of the different KV channels. Studies with channel chimeras demonstrate that NaV{beta}1-mediated changes in activation kinetics and voltage dependence of activation require interaction of NaV{beta}1 with the channel's voltage-sensing domain, whereas changes in inactivation and deactivation require interaction with the channel's pore domain. A molecular model based on docking studies shows NaV{beta}1 lying in the crevice between the voltage-sensing and pore domains of KV channels, making significant contacts with the S1 and S5 segments. Cross-modulation of NaV and KV channels by NaV{beta}1 may promote diversity and flexibility in the overall control of cellular excitability and signaling.
关键词：colocalization ; gating ; voltage-gated ion channels ; patch-clamp ; accessory subunit