The Na+-Ca2+ exchanger cardiac is essential for the action of glycosides

被引：142

作者：

Reuter, H

Henderson, SA

Han, TY

Ross, RS

Goldhaber, JI

Philipson, KD

机构：

[1] Univ Calif Los Angeles, Sch Med, Cardiovasc Res Labs, Los Angeles, CA 90095 USA

[2] Univ Calif Los Angeles, Sch Med, Dept Physiol, Los Angeles, CA 90095 USA

[3] Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90095 USA

来源：

CIRCULATION RESEARCH | 2002年 / 90卷 / 03期

关键词：

Na+-Ca2+ exchange; cardiac glycosides; genetically altered mice;

D O I：

10.1161/hh0302.104562

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

The widely accepted model to explain the positive inotropic effect of cardiac glycosides invokes altered Na+-Ca2+ exchange activity secondary to Na+ pump inhibition. However, proof of this model is lacking and alternative mechanisms have been proposed. We directly tested the role of the Na+-Ca2+ exchanger in the action of the glycoside ouabain using Na+-Ca2+ exchanger knockout mice. Ablation of the exchanger is embryonic lethal, but contractility can be studied in embryonic heart tubes at day 9.5 postcoitum. Heart tubes isolated from homozygous Na+-Ca2+ exchanger knockout mice (NCX-/-) display surprisingly normal Ca2+ transients. Removal of extracellular Na+ induces Ca2+ overload in wild-type heart tubes but does not alter the Ca2+ transients of NCX-/- heart tubes. Similarly, ouabain, at levels causing Ca2+ overload in wild-type heart tubes, has no effect on NCX-/- heart tubes. We conclude that in embryonic mouse myocytes the Na+-Ca2+ exchanger is absolutely required for the effect of cardiac glycosides on Ca-i(2+).

引用

页码：305 / 308

页数：4

共 21 条

[11] STIMULATORY EFFECT OF OUABAIN ON T-TYPE AND L-TYPE CALCIUM CURRENTS IN GUINEA-PIG CARDIAC MYOCYTES [J].