Forskolin, a new positive inotropic agent, and its influence on myocardial electrogenic cation movements.

Forskolin exerts concentration-dependent positive inotropic effects in guinea pig isolated papillary muscles; resting potential, overshoot, and upstroke velocity remain unchanged. It markedly potentiates Ca2+-mediated action potentials elicited in partially depolarized myocardial fibers (increases in upstroke velocity, height, and action potential duration) and restores slow-channel-mediated transmembrane Ca2+ influx and contractile force under conditions of external Ca2+ withdrawal or in the presence of the specific Ca2+ antagonist D 600. In partially depolarized ventricular muscle, the potentiation of transmembrane inward Ca2+ current by forskolin is correlated with a reciprocal inhibition of Mg2+-induced electrogenic membrane effects. In this respect, forskolin resembles other Ca2+ influx promoters such as beta-adrenoceptor agonists, histamine, and dibutyryl-cyclic AMP (cAMP). All these agents favor sarcolemmal Ca2+ accumulation through increases in intracellular cAMP and the subsequent formation of Ca2+-binding phosphorylated membrane proteins; Mg2+ ions seem to be displaced by Ca2+. These findings support the concept that the effects of forskolin result from an increase in intracellular cAMP.