Differential inhibition of transient outward currents of Kv1.4 and Kv4.3 by endothelin

被引：19

作者：

Hagiwara, K

Nunoki, K ^{[1
]}

Ishii, K

Abe, T

Yanagisawa, T

机构：

[1] Tohoku Univ, Grad Sch Med, Dept Mol Pharmacol, Sendai, Miyagi 980, Japan

[2] Yamagata Univ, Sch Med, Dept Pharmacol, Yamagata 990, Japan

[3] Tohoku Univ, Grad Sch Med, Div Nephrol Endocrinol & Vasc Med, Dept Med, Sendai, Miyagi 980, Japan

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2003年 / 310卷 / 02期

基金：

日本学术振兴会;

关键词：

Kv1.4; Kv4.3; transient outward current; endothelin; ventricular arrhythmia; heart failure; PKC; CaMKII; phosphorylation; mutagenesis;

D O I：

10.1016/j.bbrc.2003.09.062

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The effects of endothelin on the transient outward K+ currents were compared between Kv1.4 and Kv4.3 channels in Xenopus oocytes expression system. Both transient outward K+ Currents were decreased by stimulation of endothelin receptor ETA coexpressed with the K+ channels. Transient outward current of Kv1.4 was decreased by about 85% after 10(-8) M ET-1, while that of Kv4.3 was decreased by about 60%. By mutagenesis experiments we identified two phosphorylation sites of PKC and CaMKII in Kv1.4 responsible for the decrease in I-to by ET-1. In Kv4.3 a PKC phosphorylation site was identified which is in part responsible for the decrease in I-to. Differences in the suppression of I-to could be ascribed to the difference in intracellular signaling including the number of phosphorylation sites. These findings might give clues for the understanding of molecular mechanism of ventricular arrhythmias in heart failure, in which endothelin is involved in the pathogenesis. (C) 2003 Elsevier Inc. All rights reserved.

引用

页码：634 / 640

页数：7

共 35 条

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[Anonymous], [No title captured]

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