Stimulation of cardiac alpha receptors increases Na/K pump current and decreases gK via a pertussis toxin-sensitive pathway.
Alpha-adrenergic amines exert concentration-dependent actions on the automaticity of cardiac Purkinje fibers (Posner, P., E. L. Farrar, and C. R. Lambert. 1976. Am. J. Physiol. 231:1415-1420; Rosen, M. R., A. J. Hordof, J. P. Ilvento, and P. Danilo, Jr. 1977. Circ. Res. 40:390-400; Rosen, M. R., R. M. Weiss, and P. Danilo, Jr. 1984. J. Pharmacol. Exp. Ther. 231:1415-1420). At high concentrations they induce a largely beta adrenergic increase in the spontaneous firing rate of adult canine Purkinje fibers, whereas at concentrations less than 10(-6) M, their effect is mediated through alpha-adrenergic receptors and is seen predominantly as a decrease in the fibers' spontaneous firing rate. The mechanism for this decrease in spontaneous firing rate remains unexplained. We report here that phenylephrine (10(-7) M) increases the activity of the Na/K pump and decreases background gK in Purkinje myocytes. Both effects appear to be alpha-1 adrenergic and, in addition, are abolished on pretreatment with pertussis toxin. These results suggest that like the atrial muscarinic receptor (Pffafinger, P. J., J. M. Martin, D. D. Hunter, N. M. Nathanson, and B. Hille. 1985. Nature [Lond.]. 317:536-538; Breitwieser, G. E., and G. Szabo. 1985. Nature [Lond.]. 317:538-540) the Purkinje fiber alpha-1 receptor is coupled to background gK via a GTP-regulatory protein. Further, they suggest that the phenylephrine-induced decrease in spontaneous firing rate is due to stimulation of the Na/K pump via a novel coupling of the Na/K pump to a pertussis toxin-sensitive GTP regulatory protein.
Shah
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Department of Physiology and Biophysics, State University of New York, Stony Brook 11794-8661.
Cohen
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Rosen
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D000818:Animals; D004285:Dogs; D004553:Electric Conductivity; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D037342:Pertussis Toxin; D010656:Phenylephrine / Q000494:pharmacology*; D011690:Purkinje Fibers / Q000187:drug effects / Q000502:physiology; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D011942:Receptors, Adrenergic, alpha; D010566:Virulence Factors, Bordetella; D010656:Phenylephrine; D037342:Pertussis Toxin; D000254:Sodium-Potassium-Exchanging ATPase