Myocardial transmembrane potentials and adrenergic receptors.
The role of adrenergic amines in the genesis of cardiac arrhythmias is well known. Electrophysiological techniques of recording intracellular potentials have led to a better understanding of the cellular mechanisms by which these amines may induce arrhythmias. Stimulation of beta 1-adrenoreceptors increases automaticity, shortens action potential duration (APD), and may enhance slow action potential (AP) formation in depolarized Purkinje fibers (PF). Excitation of alpha-adrenoreceptors prolongs repolarization and plateau phase in PF. On the basis of the spectrum of antiarrhythmic activity in vivo and qualitatively different transmembrane effects on the canine PF, beta-adrenoreceptor blocking drugs can be subdivided into two distinct categories. Recent evidence with two new highly selective beta blockers, PS-6 and mepindolol, also suggests that at least two subgroups of cardiac beta 1-adrenoreceptors can be differentiated: beta 1i for inotropic and beta 1c for chrontropic actions of catecholamines. The effects of PS-6 in 5 x 10(-5) M concentration on isolated rabbit atria showed that this agent atangonized ouabain-induced arrhythmias and contracture. PS-6 (8 x 10(-6) M or more) reduced AP amplitude, phase 0 depolarization, APD, and phase 2 plateau phase in paced canine PF. These data suggest that PS-6 exerts a direct transmembrane effect on the canine PF.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced; D006339:Heart Rate / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects*; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium; D010042:Ouabain / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D011690:Purkinje Fibers / Q000187:drug effects; D011817:Rabbits; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*
D011412:Propanolamines; D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D010042:Ouabain; C025707:PS-6; D007545:Isoproterenol