title: Voltage-dependent Vmax blockade in Na+-dependent action potentials after beta 1- and H2-receptor stimulation in mammalian ventricular myocardium.
abstract: In isolated papillary muscles of guinea pigs, the influence of isoproterenol, histamine, theophylline, and phenylephrine on the maximal rate of rise (Vmax) of Na+-dependent action potentials and on isometric contractile force was studied under rested state conditions. Isoproterenol (1 x 10(-7) mol/L), histamine (2 x 10(-5) mol/L), and theophylline (2 x 10(-3) mol/L) shifted the voltage dependence of Vmax into the hyperpolarizing direction and, consequently, led to a voltage-dependent Vmax blockade. The alpha-adrenoceptor agonist phenylephrine, on the other hand, proved to be ineffective in depressing Vmax. The beta-receptor blocker pindolol (4 x 10(-6) mol/L) or the H2-receptor blocker cimetidine (4 x 10(-5) mol/L) abolished the inhibitory effects of isoproterenol and histamine, respectively, and caused Vmax to return to the initial control value. A concentration-response relationship analysis at -65 mV revealed that isoproterenol exerted only a weak inhibitory effect on Vmax compared with its positive inotropic action. The IC50 value of the former effect amounted to approximately 5 x 10(-6) mol/L, but the EC50 value of the latter effect was 4 x 10(-8) mol/L. It is, therefore, concluded that, in physiologically relevant concentrations, beta-adrenergic agonists are unlikely to significantly modulate Na+-dependent excitability even in partially depolarized myocardium.
authors.affiliation: Physiological Institute, University Freiburg, West Germany.
authors.forename: A M
authors.initials: AM
authors.lastname: Gillis
authors.forename: M
authors.initials: M
authors.lastname: Kohlhardt
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D005260:Female; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000187:drug effects; D006632:Histamine / Q000494:pharmacology*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D010210:Papillary Muscles / Q000187:drug effects / Q000502:physiology*; D010656:Phenylephrine / Q000494:pharmacology*; D012964:Sodium / Q000494:pharmacology*; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology*; D013806:Theophylline / Q000494:pharmacology*; D016276:Ventricular Function
chemical_list: D015222:Sodium Channels; D010656:Phenylephrine; D006632:Histamine; D012964:Sodium; D013806:Theophylline; D007545:Isoproterenol