Ouabain induced Ca2+ overload in wild-type embryonic heart tubes but had no effect on Na+-Ca2+ exchanger knockout (NCX-/-) heart tubes.
This preclinical study provides direct evidence that the Na+-Ca2+ exchanger is absolutely required for the intracellular calcium-modulating effects of cardiac glycosides.
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 Ca2+(i).
Reuter et al. (Fri,) reported a other. Ouabain vs. Wild-type heart tubes was evaluated on Ca2+ transients and Ca2+ overload. Ouabain induced Ca2+ overload in wild-type embryonic heart tubes but had no effect on Na+-Ca2+ exchanger knockout (NCX-/-) heart tubes.