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


CONCLUSIONS
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.
Burashnikov
A
A
Masonic Medical Research Laboratory, Utica, NY 13501, USA.
Antzelevitch
C
C
D000200:Action Potentials / Q000187:drug effects*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D004146:Dioxanes / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004699:Endocardium / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects*; D066298:In Vitro Techniques; D008729:Methoxamine / Q000494:pharmacology*; D008839:Microelectrodes; D010496:Pericardium / Q000187:drug effects; D010656:Phenylephrine / Q000494:pharmacology*; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011690:Purkinje Fibers / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D004146:Dioxanes; D010656:Phenylephrine; C051731:chlorethylclonidine; D011433:Propranolol; C010654:(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane; D008729:Methoxamine; D003000:Clonidine; D011224:Prazosin