Electrical and mechanical effects of anthopleurin-A, a polypeptide from a sea anemone, on isolated rabbit ventricular muscle under conditions of hypoxia and glucose-free medium.

The effects of anthopleurin-A (AP-A, 1 x 10(-8) M) on the membrane action potential and contraction of isolated rabbit ventricular muscle were compared with those of ouabain (5 x 10(-7) M). Under control conditions, AP-A and ouabain showed submaximal (about 80% of maximal) positive inotropic effects without any toxic manifestations. AP-A caused a marked prolongation of action potential duration (APD) without affecting any other parameters of the action potential, whereas ouabain caused a shortening of APD and a slight decrease in maximum diastolic potential (MDP), overshoot (OS), and upstroke velocity (dV/dtmax) of the action potential. The positive inotropic effect of AP-A was relatively well maintained even under hypoxia or in glucose-free medium. Under these abnormal experimental conditions, AP-A caused a prolongation of APD only at the late stage of repolarization (APD80), whereas APD at the early stage of repolarization (APD30) was further shortened. Other parameters of action potential and resting tension (RT) were not influenced by AP-A. In contrast, under similar experimental conditions, ouabain caused no apparent positive inotropic action, but resulted in a marked increase in RT (contracture). In addition, after exposure to ouabain, a progressive shortening of APD and marked decreases in MDP, OS, and dV/dtmax were observed. These results indicate the AP-A has pharmacological properties quite different from those of ouabain and suggest possible advantages of this newly developed cardiotonic agent over cardiac glycosides when acting on the energy-depleted myocardium.