Differences in the electrophysiologic response of four canine ventricular cell types to alpha 1-adrenergic agonists

The present study was designed to examine regional differences in the response of alpha 1 adrenoceptor stimulation in the canine ventricle.

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.

Phenylephrine (0.1-10 microM+ propranolol 0.2 microM) and methoxamine (1-10 microM) produced dose- and rate-dependent prolongation of action potential duration (APD90) in Purkinje fibers (P < 0.05, at 0.1-10 microM, BCL = 0.5-2 s), but an abbreviation of APD90 in tissues from the M region (P < 0.05, at 10 microM, BCL = 0.5-2 s). At slow pacing rates (> or = 2 s), phenylephrine (1 microM) exerted a small, significant (P < 0.05) prolongation of APD90 in epicardium and endocardium which returned to control values when the concentration was increased to 10 microM. The amplitude of phase 1 of the action potential in M and epicardial cells was significantly increased by phenylephrine at concentrations of 10 microM (P < 0.05). Prazosin (1 microM), a nonspecific alpha 1 antagonist, reversed these effects of phenylephrine (10 microM) and methoxamine (10 microM) on APD90 and the action potential notch. The alpha 1b-antagonist, chloroethylclonidine (0.1-1.0 microM), but not the alpha 1a-antagonist, WB-4101 (0.1-1.0 microM), reversed the APD-abbreviating effect of methoxamine in the M cell.

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.