期刊
CIRCULATION RESEARCH
卷 90, 期 3, 页码 305-308出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/hh0302.104562
关键词
Na+-Ca2+ exchange; cardiac glycosides; genetically altered mice
资金
- NHLBI NIH HHS [HL 48509] Funding Source: Medline
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+).
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