The dual effects of ouabain on 45Ca2+ transport and contractility in adult rat ventricular myocytes.

We used isolated ventricular myocytes to study 45Ca2+ transport in the presence of three concentrations of ouabain (10 nM, 1 microM, and 100 microM) in Tyrode solution containing 1 mM CaCl2. The cells were quiescent and during 45Ca2+ uptake and 45Ca2+ efflux experiments, 10 nM ouabain decreased Ca2+ content, 1 microM, didn't change it appreciably, and 100 microM increased it significantly. Qualitatively, the same results were obtained at 22 degrees C and 35 degrees 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 (less than or equal to 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.