Open AccessThe Na + -Ca 2+ Exchanger Is Essential for the Action of Cardiac Glycosides
Author(s) -
Hannes Reuter,
Scott A. Henderson,
Tie-Yan Han,
Robert S. Ross,
Joshua I. Goldhaber,
Kenneth D. Philipson
Publication year - 2002
Publication title -
circulation research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.899
H-Index - 336
eISSN - 1524-4571
pISSN - 0009-7330
DOI - 10.1161/hh0302.104562
Subject(s) - contractility , ouabain , inotrope , chemistry , embryonic heart , myocyte , sodium calcium exchanger , extracellular , medicine , endocrinology , biophysics , embryonic stem cell , intracellular , biochemistry , biology , sodium , gene , organic chemistry
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).
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