Localization of beta adrenergic receptors, and effects of noradrenaline and cyclic nucleotides on action potentials, ionic currents and tension in mammalian cardiac muscle.
1. Isoprenaline and noradrenaline were applied iontophoretically to cardiac Purkinje fibres. Intracellular application of the drugs had no effect, while extracellular application of the same amounts of charge caused acceleration of pace-maker activity and a shift of the plateau level of the action potential. These results indicate that beta-adrenergic receptors are located at the outside of the cardiac cell membrane.2. A systematic comparison of the effects of cyclic AMP derivatives and noradrenaline on action potentials and isometric tension of ventricular myocardial preparations showed that the nucleotides and the catecholamine increase the plateau height and the duration of the action potential and also increase tension. However, there are quantitative differences in the action of these drugs.3. Cyclic AMP derivatives and noradrenaline increase the slow inward current, I(Ca), in ventricular myocardial preparations. Voltage clamp analysis of I(Ca) showed that the kinetic parameters of this membrane current are not affected by these drugs. However, the membrane conductance to Ca ions is greatly increased by noradrenaline and to a smaller extent by dibutyryl cyclic AMP.4. Concentration-response relations of the membrane effects of noradrenaline on plateau height of the action potential and on I(Ca) could be fitted by the same theoretical log concentration-response curve. The Hill plot of this concentration-response curve had a slope of 2. The half maximal response occurred at 5 x 10(-7)M.5. The results are compared with other membrane effects of catecholamines and cyclic nucleotides in cardiac muscle. The effects on I(Ca) are related to the positive inotropic effect of the drugs.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002415:Cats; D002417:Cattle; D000242:Cyclic AMP / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004553:Electric Conductivity; D006321:Heart / Q000187:drug effects*; D006329:Heart Conduction System / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007478:Iontophoresis; D007545:Isoproterenol / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009638:Norepinephrine / Q000008:administration & dosage / Q000494:pharmacology*; D011690:Purkinje Fibers / Q000187:drug effects*; D011941:Receptors, Adrenergic; D013268:Stimulation, Chemical; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors
D011941:Receptors, Adrenergic; D013779:Tetrodotoxin; D003994:Bucladesine; D000242:Cyclic AMP; D007545:Isoproterenol; D009638:Norepinephrine