Modulation of ventricular action potential by alpha 1-adrenoceptors and protein kinase C.
The effects of the alpha 1-adrenoceptor agonist methoxamine (MTX) and the direct protein kinase C (PKC) activator phorbol 12,13-dibutyrate (PDBU) on action potentials from guinea pig papillary muscles were studied. Measured with conventional microelectrodes, MTX (1 x 10(-7) to 3 x 10(-4) M) and PDBU (1 x 10(-9) to 1 x 10(-6) M) both caused a dose-dependent and reversible decrease in the action potential duration measured at 90% repolarization (APD90) at 36.5 degrees C. The MTX-mediated response was blocked by both prazosin (3 x 10(-6) M) and phentolamine (1 x 10(-6) M) and mimicked by phenylephrine. Maximal concentrations of the two agents together resulted in only a partial (50%) additive decrease in the APD90. At a lower temperature (27.5 degrees C), PDBU no longer produced a shortening in the APD90 and MTX produced a prolongation in the APD90. These results demonstrate that although alpha 1-adrenoceptor stimulation and PKC activation in guinea pig papillary muscle both lead to a decrease in the APD90, the differences in their effects as related to the magnitude, partial additivity, and temperature dependence suggest that the mechanism of action are not identical. These subtle differences may help to delineate the exact physiological implications of alpha 1-adrenoceptors in cardiac excitation and contraction.
Dirksen
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RT
Department of Pharmacology, University of Rochester School of Medicine and Dentistry, New York 14642.
Sheu
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SS
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D004357:Drug Synergism; D004558:Electric Stimulation; D006168:Guinea Pigs; D006352:Heart Ventricles; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D009994:Osmolar Concentration; D010210:Papillary Muscles / Q000502:physiology*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011493:Protein Kinase C / Q000494:pharmacology*; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D013696:Temperature
D011942:Receptors, Adrenergic, alpha; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C; D008729:Methoxamine