The dual effects of ouabain on45Ca2+ transport and contractility in adult rat ventricular myocytes

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Abstract
We used isolated ventricular myocytes to study45Ca2+ transport in the presence of three concentrations of ouabain (10 nM, 1 μM, and 100 μM) in Tyrode solution containing 1 mM CaCl2. The cells were quiescent and during45Ca2+ uptake and45Ca2+ efflux experiments 10 nM ouabain decreased Ca2+ content, 1 μM, didn't change it appreciably, and 100 μM increased it significantly. Qualitatively, the same results were obtained at 22°C and 35°C. Ouabain did not significantly affect the electrical activity of isolated, electrically stimulated myocytes, but it increased the amplitude of shortenings of these myocytes in a dose-dependent manner. Thus, the positive inotropic effect of ouabain at therapeutic doses (≤10 nM) occurs in spite of decreased Ca2+ content, while at high toxic doses the positive inotropic effect is accompanied by an increment in Ca2+ content. These data support the hypothesis that the mechanisms of positive inotropy of ouabain are different at therapeutic and toxic concentrations of this drug. Finally, our study demonstrates that the effects of low doses of ouabain are independent of the release of endogenous catecholamines.