Different effects of isoproterenol and dihydroouabain on cardiac Ca2+ transients

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