Mechanisms for the α-Adrenoceptor-Mediated Positive Inotropy in Mouse Ventricular Myocardium: Enhancing Effect of Action Potential Prolongation

Abstract

Mechanisms for the α-adrenoceptor-mediated positive inotropy in neonatal mouse ventricular myocardium were studied with isolated myocardial preparations. The phenylephrine-induced positive inotropy was suppressed by prazosin, nifedipine, and chelerythrine, a protein kinase C inhibitor, but not by SEA0400, a selective Na+/Ca2+ exchanger inhibitor. Phenylephrine increased the L-type Ca2+ channel current and prolonged the action potential duration, while the voltage-dependent K+ channel current was not influenced. In the presence of cromakalim, an ATP-sensitive K+ channel opener, the phenylephrine-induced prolongation of action potential duration, as well as the positive inotropy, were smaller than in the absence of cromakalim. These results suggest that the α-adrenoceptor-mediated positive inotropy is mediated by an increase in Ca2+ influx through the L-type Ca2+ channel, and the concomitant increase in action potential duration acts as an enhancing factor.

Molecular Mechanisms of Cardiac Development and Disease

“…By evaluating the effects of different antihypertensive drugs on isolated neonatal mouse ventricles, the authors suggest that α-adrenoceptor-mediated positive inotropy is mediated by an increase in Ca 2+ influx through the L-type Ca 2+ channel. Furthermore, α-adrenoceptor-mediated positive inotropy was accompanied by prolongation of action potential duration, which in turn enhanced α-adrenoceptor-mediated positive inotropy [7]. In this Special Issue, Rosemary F. Kelly's group investigated the effects of placing an adjuvant mesenchymal stem cell patch during coronary artery bypass surgery (CABG) [8].…”