Positive inotropic effects of ouabain in isolated cat ventricular myocytes in sodium-free conditions

Manabu Nishio, Stuart W. Ruch, J. Andrew Wasserstrom

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

The inotropic and toxic effects of cardiac steroids are thought to result from Na+-K+-ATPase inhibition, with elevated intracellular Na+-(Nai+)causing increased intracellular Ca2+(Cai2+) via Na-Ca exchange. We studied the effects of ouabain on cat ventricular myocytes in Na+-free conditions where the exchanger is inhibited. Cell shortening and Cai2+ transients (with fluo 4-AM fluorescence) were measured under voltage clamp during exposure to Na+-free solutions [LiCl or N-methyl-D-glucamine (NMDG) replacement]. Ouabain enhanced contractility by 121 ± 55% at 1 μmol/l (n = 11) and 476 ± 159% at 3 μmol/l (n = 8) (means ± SE). Cai2+ transient amplitude was also increased. The inotropic effects of ouabain were retained even after pretreatment with saxitoxin (5 μmol/l) or changing the holding potential to - 40 mV (to inactivate Na+ current). Similar results were obtained with both Li+ and NMDG replacement and in the absence of external K+, indicating that ouabain produced positive inotropy in the absence of functional Na-Ca exchange and Na+-K+-ATPase activity. In contrast, ouabain had no inotropic response in rat ventricular myocytes (10-100 μmol/l). Finally, ouabain reversibly increased Ca2+ overload toxicity by accelerating the rate of spontaneous aftercontractions (n = 13). These results suggest that the cellular effects of ouabain on the heart may include actions independent of Na+-K+-ATPase inhibition, Na-Ca exchange, and changes in Nai+.

Original languageEnglish (US)
Pages (from-to)H2045-H2053
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume283
Issue number5 52-5
DOIs
StatePublished - Nov 1 2002

Keywords

  • Cardiac glycosides
  • Digitalis toxicity
  • N-methyl-D-glucamine
  • Sarcoplasmic reticulum

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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