The Na -Ca Exchanger Is Essential for the Action of Cardiac Glycosides
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چکیده
The widely accepted model to explain the positive inotropic effect of cardiac glycosides invokes altered Na -Ca 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 -Ca exchanger in the action of the glycoside ouabain using Na -Ca 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 -Ca exchanger knockout mice (NCX / ) display surprisingly normal Ca transients. Removal of extracellular Na induces Ca overload in wild-type heart tubes but does not alter the Ca transients of NCX / heart tubes. Similarly, ouabain, at levels causing Ca overload in wild-type heart tubes, has no effect on NCX / heart tubes. We conclude that in embryonic mouse myocytes the Na -Ca exchanger is absolutely required for the effect of cardiac glycosides on Ca i. (Circ Res. 2002;90:305-308.)
منابع مشابه
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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...
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تاریخ انتشار 2002