| First Author | Reuter H | Year | 2002 |
| Journal | Circ Res | Volume | 90 |
| Issue | 3 | Pages | 305-8 |
| PubMed ID | 11861419 | Mgi Jnum | J:103484 |
| Mgi Id | MGI:3609572 | Doi | 10.1161/hh0302.104562 |
| Citation | Reuter H, et al. (2002) The Na+-Ca2+ exchanger is essential for the action of cardiac glycosides. Circ Res 90(3):305-8 |
| abstractText | 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). |
