Requirement of a macromolecular signaling complex for β adrenergic receptor modulation of the KCNQ1-KCNE1 potassium channel

被引：564

作者：

Marx, SO ^{[1
]}

Kurokawa, J ^{[1
]}

Reiken, S ^{[1
]}

Motoike, H ^{[1
]}

D'Armiento, J ^{[1
]}

Marks, AR ^{[1
]}

Kass, RS ^{[1
]}

机构：

[1] Columbia Univ Coll Phys & Surg, Dept Med, Ctr Mol Cardiol, Dept Pharmacol, New York, NY 10032 USA

来源：

SCIENCE | 2002年 / 295卷 / 5554期

关键词：

D O I：

10.1126/science.1066843

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Sympathetic nervous system (SNS) regulation of cardiac action potential duration (APD) is mediated by beta adrenergic receptor (betaAR) activation, which increases the stow outward potassium ion current (I-Ks). Mutations in two human I-Ks channel subunits, hKCNQ1 and hKCNE1, prolong APD and cause inherited cardiac arrhythmias known as LQTS (long QT syndrome). We show that PAR modulation of I-Ks requires targeting of adenosine 3',5'-monophosphate (cAMP)dependent protein kinase (PKA) and protein phosphatase 1 (PP1) to hKCNQ1 through the targeting protein yotiao. Yotiao binds to hKCNQ1 by a leucine zipper motif, which is disrupted by an LQTS mutation (hKCNQ1-G589D). Identification of the hKCNQ1 macromolecular complex provides a mechanism for SNS modulation of cardiac APD through I-Ks.

引用

页码：496 / 499

页数：4

共 20 条

[1] β2-adrenergic receptor overexpression in the developing mouse heart:: evidence for targeted modulation of ion channels [J].