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I(Ks) 通道复合物中 K(V)7.1-KCNE(x) 相互作用的结构基础。

Structural basis for K(V)7.1-KCNE(x) interactions in the I(Ks) channel complex.

机构信息

Danish National Research Foundation Centre for Cardiac Arrhythmia, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.

出版信息

Heart Rhythm. 2010 May;7(5):708-13. doi: 10.1016/j.hrthm.2009.12.017. Epub 2009 Dec 24.

Abstract

The cardiac I(Ks) current is involved in action potential repolarization, where its primary function is to limit action potential prolongation during sympathetic stimulation. The I(Ks) channel is mainly composed of K(V)7.1 ion channels associated with KCNE1 auxiliary subunits. The availability of KCNE1 solution structure by nuclear magnetic resonance spectroscopy in conjunction with biochemical assays addressing K(V)7.1-KCNE1 residue interactions has provided new insights into the structural basis for K(V)7.1 modulation by KCNE1. Recent evidence further suggests that KCNE2 may associate with the K(V)7.1-KCNE1 channel complex and modulate its current amplitude. Here we review recent studies in this area and discuss potential roles for multiple KCNE(x) subunits in I(Ks) generation and modulation as well as the clinical relevance of the new information.

摘要

心脏 I(Ks)电流参与动作电位复极化,其主要功能是在交感神经刺激期间限制动作电位的延长。I(Ks)通道主要由 K(V)7.1 离子通道与 KCNE1 辅助亚基组成。通过核磁共振波谱学获得 KCNE1 溶液结构的可用性,并结合生化测定解决 K(V)7.1-KCNE1 残基相互作用的问题,为 K(V)7.1 由 KCNE1 调节的结构基础提供了新的见解。最近的证据进一步表明,KCNE2 可能与 K(V)7.1-KCNE1 通道复合物结合并调节其电流幅度。本文综述了该领域的最新研究,并讨论了多个 KCNE(x)亚基在 I(Ks)产生和调节中的潜在作用以及新信息的临床相关性。

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