The inotropic actions of adrenaline on frog ventricular muscle: relaxing versus potentiating effects

Abstract

In frog ventricle, adrenaline [epinephrine] increases the size of the action potential, potentiates twitch tension and enhances relaxation. Because tension development is directly controlled by membrane potential in frog ventricle, experiments were designed to separate the effects of adrenaline on the action potential from its effects on the development of tension. Comparison of the tension-voltage relations in the presence and absence of adrenaline showed that during the initial portion of the voltage clamp step, adrenaline potentiated tension, but beyond 1 s into the clamp pulse tension was depressed. Ni2+, which blocks the slow inward current in frog ventricle, inhibited the positive inotropic effect of adrenaline. The relaxant effect of adrenaline was present at least as early as 600 ms after the onset of membrane depolarization. Generally 1 s or more of membrane depolarization was required before the relaxant effect of adrenaline predominated over its positive inotropic effect. In catecholamine depleted strips, the augmentation of the action potential and twitch tension in the presence of adrenaline occurred at a 60-fold lower concentration than the relaxant effect as judged by suppression of KCl-induced contractures. Pure .beta.-receptor agonists completely reproduced the electromechanical effects of adrenaline on the frog ventricle. .beta.-Receptor agonists or antagonists had no effect on action potential or development of tension. cAMP and dibutyryl cAMP augmented the frog ventricular action potential and potentiate twitch tension in reserpinized or .beta.-blocked frog ventricular strips. No relaxant effect of catecholamines was reproduced by these agents alone. Theophylline produced changes in the action potential similar to those induced by adrenaline and mimicked the positive inotropic and relaxant effects of the drug. The positive inotropic effects of adrenaline apparently results mainly from changes induced in the action potential plateau. The changes are time and voltage dependent, and if inhibited, leave the relaxant effect of adrenaline unopposed. The findings are consistent with a cAMP-mediated mechanism of the positive inotropic effect of adrenaline. The role of cAMP in mediating the relaxant effects of adrenaline is less clear.