Role of mitochondrial dysfunction in cardiac glycoside toxicity.

ABSTRACT: Cardiac glycosides, which inhibit the plasma membrane Na(+) pump, are one of the four categories of drug recommended for routine use to treat heart failure, yet their therapeutic window is limited by toxic effects. Elevated cytoplasmic Na(+) ([Na(+)](i)) compromises mitochondrial energetics and redox balance by blunting mitochondrial Ca(2+) ([Ca(2+)](m)) accumulation, and this impairment can be prevented by enhancing [Ca(2+)](m). Here, we investigate whether this effect underlies the toxicity and arrhythmogenic effects of cardiac glycosides and if these effects can be prevented by suppressing mitochondrial Ca(2+) efflux, via inhibition of the mitochondrial Na(+)/Ca(2+) exchanger (mNCE). In isolated cardiomyocytes, ouabain elevated [Na(+)](i) in a dose-dependent way, blunted [Ca(2+)](m) acc

SUBMITTER: Liu T 

PROVIDER: S-EPMC2949492 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature