Adrenoceptors in cardiac ventricular muscle and changes in duration of action potential caused by noradrenaline and isoprenaline.
1. On guinea-pig papillary muscle we investigated whether a prolonging effect of noradrenaline on the duration of the cardiac ventricular action potential (AP) is attributable to an action on beta-adrenoceptors. 2. Propranolol (5 X 10(-6) M), which itself shortens AP (at 90% repolarization level), inhibits both effects of noradrenaline on the AP, i.e. the sustained prolongation by low concentrations (10(-7)--10(-6)M) and the steady-state shortening which follows an initial prolongation by a high concentration (10(-5)M). In the presence of propranolol, the prlonging effect of noradrenaline is shifted to higher concentrations (10(-6)--10(-5)M). This prolongation of AP duration does not exceed the prior shortening effect by propranolol; it is not prevented by 10(-5)M phentolamine. 3. Phentolamine, which itself prolongs AP duration, inhibits neither the initial prolongation nor the steady-state shortening of the AP by 10(-5)M noradrenaline. Instead, the biphasic change in AP duration as well as the positive inotropic effect of 10(-5)M noradrenaline are enhanced in the presence of 3Z10(-6)M phentolamine. 4. The effect of isoprenaline on the duration of AP qualitatively resembles that of noradrenaline. In a concentration of 10(-8)M, isoprenaline produces a sustained prolongation of the AP; concentrations of 10(-7)M and 10(-6)M cause an initial prolongation which is followed by a steady-state shortening. These effects are inhibited by propranolol. 5. It is concluded that not only the steady-state shortening effect on AP duration by 10(-5)M noradrenaline but also the prolongation of AP, induced by lower noradrenaline concentrations (10(-7)--10(-6)M), are mediated solely by an action on beta-adrenoceptors.
D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D004558:Electric Stimulation; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000187:drug effects*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology*; D010210:Papillary Muscles / Q000378:metabolism / Q000502:physiology; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011941:Receptors, Adrenergic / Q000187:drug effects*; D013997:Time Factors
D011941:Receptors, Adrenergic; D011433:Propranolol; D007545:Isoproterenol; D009638:Norepinephrine; D010646:Phentolamine