Different effects of isoproterenol and dihydroouabain on cardiac Ca2+ transients.

Cytosolic fura-2 Ca2+ transient signals (TCa) and the left ventricular pressure or contraction of myocardium under the positive inotropic effects of the beta-adrenoceptor agonist, isoproterenol, and the cardiac glycoside, dihydroouabain, were measured simultaneously and the results were compared. TCa was observed preceding the onset of force development and showed a steeper rise and slower decay than did the contraction curve of papillary muscle. Isoproterenol increased the steepness and the amplitude of TCa, reflecting the speed and peak force of contraction, and clearly biphasic TCa were observed with biphasic contractions developed at low frequency. Ryanodine reduced not only the early component of the contraction but also TCa, without affecting the diastolic Ca2+ level. These effects of isoproterenol were attributed to the enhanced uptake of Ca2+ by the sarcoplasmic reticulum. In contrast, dihydroouabain elevated the Ca2+ level at diastole without any change in the amplitude of TCa, suggesting that dihydroouabain inhibits the membrane Na pump thereby increasing the intracellular Ca2+ via Na(+)-Ca2+ exchange. Furthermore, a comparison of the time course of the isometric twitch curve with that of TCa in rested state contraction indicated that there are distinct differences between the mechanisms of the positive inotropic effects of isoproterenol and of dihydroouabain.