Electrophysiological effects of endothelin-1 on canine myocardial cells.
Endothelin-1 (ET-1) has been shown to induce severe ventricular arrhythmias associated with myocardial ischemia. However, ET-1 may have a direct arrhythmogenic action that is not related to myocardial ischemia. To examine this possibility, we studied the electrophysiological effects of ET-1 on cardiac tissues. The right bundle branch, false tendon, ventricular muscle, and atrial muscle were isolated from the dog, and transmembrane potentials were recorded by the conventional microelectrode technique. ET-1 prolonged the action potential duration (APD) in all of the tissues tested except in the atrial muscle, where the APD was shortened. Bay K 8644, a calcium channel agonist, prolonged the APD in all cardiac tissues. Spontaneous firing of the right bundle branch was suppressed by ET-1 but not Bay K 8644. The prolongation of the APD by ET-1 was far more marked in the right bundle branch than in other tissues, and it was followed by the development of early after depolarizations (EADs) only in the right bundle branch. The EADs induced by ET-1 or Bay K 8644 were abolished by nicardipine. These data suggest that L-type calcium current is involved in the genesis of EADs by ET-1, although other ionic mechanisms can not be ruled out. Since EADs underlie some types of arrhythmias, arrhythmias caused by ET-1 are at least partly attributable to the direct actions of the agent on myocardial cells.
Yorikane
R
R
Biological Research Laboratories, Sankyo Co., Ltd., Tokyo, Japan.
Koike
H
H
Miyake
S
S
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000503:physiopathology; D004285:Dogs; D016232:Endothelins / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects
D016232:Endothelins; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester