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.