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.
Vogel
S M
SM
Department of Pharmacology, University of Illinois College of Medicine, Chicago 60612.
Terzic
A
A
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002415:Cats; D002712:Chlorides / Q000494:pharmacology; D004594:Electrophysiology; D004837:Epinephrine / Q000494:pharmacology; D006321:Heart / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D066298:In Vitro Techniques; D008094:Lithium / Q000494:pharmacology; D018021:Lithium Chloride; D009206:Myocardium / Q000166:cytology; D011188:Potassium / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
D002712:Chlorides; D011942:Receptors, Adrenergic, alpha; D008094:Lithium; D011433:Propranolol; D018021:Lithium Chloride; D011188:Potassium; D011224:Prazosin; D004837:Epinephrine