期刊
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
卷 42, 期 4, 页码 760-768出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.yjmcc.2006.10.013
关键词
protein tyrosine kinases; epidermal growth factor receptor; protein tyrosine phosphatases; voltage-gated sodium current; ion channels; guinea pig ventricular myocytes; heart
Voltage-gated cardiac fast sodium channel current (I-Na) plays a critical role in the initiation and propagation of the myocardial action potential, and regulation of cardiac I-Na by protein tyrosine kinases (PTKs) is not well documented, though it is known that ion channels are among the targets of PTKs. The present study was therefore designed to investigate whether/how cardiac I-Na was modulated by PTKs in guinea pig ventricular myocytes using whole-cell patch clamp and immunoprecipitation and Western blotting approaches. It was found that cardiac I-Na was enhanced by epidermal growth factor (EGF), and the effect was antagonized by the selective epidermal growth factor receptor (EGFR) kinase inhibitor tyrphostin AG556 while potentiated by orthovanadate (a protein tyrosine phosphatase (PTP) inhibitor). In addition, AG556 inhibited, while orthovanadate increased I-Na, and the inhibition of I-Na by AG556 was antagonized by orthovanadate. Immumoprecipitation and Western blotting analysis demonstrated that tyrosine phosphorylation level of cardiac sodium channels was enhanced by EGF or orthovanadate, and reduced by AG556. The AG556-induced reduction of phosphorylation level was significantly reversed by orthovanadate. Our results demonstrate the novel information that EGFR kinase enhances, and PTPs reduce native cardiac I-Na in guinea pig ventricular myocytes. (c) 2006 Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据