Alpha-adrenergic regulation of action potentials in isolated rat cardiomyocytes

Radioligand binding studies and studies in which inositol phosphate levels were assayed have provided substantial evidence for the existence of alpha 1-adrenoceptors in isolated rat ventricular myocytes, a pure cardiac preparation free of neuronal and vascular elements. Since correlational electrophysiological studies have not been carried out in this model, we investigated alpha-adrenergic effects on action potentials using intracellular microelectrodes to impale the myocytes. Epinephrine, in the presence of propranolol (10(-6) M), rapidly increased the action potential duration in a concentration-dependent manner (threshold concentration of 30 nM, EC50 of 100 nM). The maximal upstroke velocity and overshoot of Ca2+-mediated action potentials (15 mM K+) were also increased. Epinephrine did not significantly affect the resting membrane potential. The alpha 1-adrenoceptor antagonist, prazosin (10(-7) M) blocked epinephrine's effects. LiCl (10 mM), an inhibitor of inositol-phosphate phosphatases potentiated the effects of epinephrine (30 nM). The results suggest that the isolated rat cardiomyocyte is a suitable preparation for examining the ionic and molecular mechanisms of direct alpha-adrenergic effects on the cardiac membrane.