Differences in the electrophysiologic response of four canine ventricular cell types to α1-adrenergic agonists

Objective: The present study was designed to examine regional differences in the response of alpha(1) adrenoceptor stimulation in the canine ventricle. Methods: Standard microelectrode techniques were used to record transmembrane action potentials from epicardial, M cell, and endocardial as well as Purkinje fiber preparations isolated from the canine left ventricle. Results: Phenylephrine (0.1-10 mu M + propranolol 0.2 mu M) and methoxamine (1-10 mu M) produced dose- and rate-dependent prolongation of action potential duration (APD(90)) in Purkinje fibers (P<0.05, at 0.1-10 mu M, BCL = 0.5-2 s), but an abbreviation of APD(90) in tissues from the M region (P<0.05, at 10 mu M, BCL = 0.5-2 s). At slow pacing rates (greater than or equal to 2 s), phenylephrine (1 mu M) exerted a small, significant (P<0.05) prolongation of APD(90) in epicardium and endocardium which returned to control values when the concentration was increased to 10 mu M. The amplitude of phase 1 of the action potential in M and epicardial cells was significantly increased by phenylephrine at concentrations of 10 mu M (P<0.05). Prazosin (1 mu M), a nonspecific alpha(1) antagonist, reversed these effects of phenylephrine (10 mu M) and methoxamine (10 mu M) on APD(90) and the action potential notch. The alpha(1b)-antagonist, chloroethylclonidine (0.1-1.0 mu M), but not the alpha(1a)-antagonist, WB-4101 (0.1-1.0 mu M), reversed the APD-abbreviating effect of methoxamine in the M cell. Conclusion: Our results demonstrate striking regional differences in the electrophysiological response of the four canine ventricular cell types to alpha(1) adrenergic agonists. Our data provide support for the hypothesis that different adrenoceptor subtypes underlie the opposite response of M cells (alpha(1b)-APD abbreviation) and Purkinje fibers (alpha(1a)-APD prolongation) to alpha(1)-adrenoceptor activation. (C) 1999 Elsevier Science B.V. All rights reserved.