DIFFERENT EFFECTS OF ISOPROTERENOL AND DIHYDROOUABAIN ON CARDIAC CA2+TRANSIENTS

Cytosolic fura-2 Ca2+ transient signals (T-Ca) and the left ventricula r pressure or contraction of myocardium under the positive inotropic e ffects of the beta-adrenoceptor agonist, isoproterenol, and the cardia c glycoside, dihydroouabain, were measured simultaneously and the resu lts were compared. T-Ca was observed preceding the onset of force deve lopment and showed a steeper rise and slower decay than did the contra ction curve of papillary muscle. Isoproterenol increased the steepness and the amplitude of T-Ca, reflecting the speed and peak force of con traction, and clearly biphasic T-Ca were observed with biphasic contra ctions developed at low frequency. Ryanodine reduced not only the earl y component of the contraction but also T-Ca, without affecting the di astolic 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 chang e in the amplitude of T-Ca, suggesting that dihydroouabain inhibits th e membrane Na pump thereby increasing the intracellular Ca2+ via Na+-C a2+ exchange. Furthermore, a comparison of the time course of the isom etric twitch curve with that of T-Ca in rested state contraction indic ated that there are distinct differences between the mechanisms of the positive inotropic effects of isoproterenol and of dihydroouabain.