Afterdepolarizations and triggered activity develop in a select population of cells (M cells) in canine ventricular myocardium: the effects of acetylstrophanthidin and Bay K 8644.
Early afterdepolarizations (EADs) are membrane oscillations that interrupt or retard the repolarization phase of the cardiac action potential, whereas delayed afterdepolarizations (DADs) are oscillations that arise after full repolarization. When EADs and DADs are sufficiently large to depolarize the cell membrane to its voltage threshold, they give rise to triggered action potentials, which are believed to underlie some forms of extrasystolic activity and tachyarrhythmias. EAD- and DAD-induced triggered activity have been described and well characterized in isolated Purkinje fibers exposed to a wide variety of drugs, but are rarely seen in syncytial preparations of ventricular myocardium. These results are inconsistent with those of in vivo studies or experiments involving enzymatically dissociated myocytes. In the present study, we used the cardiotonic agent acetylstrophanthidin (AcS) and the calcium channel agonist Bay K 8644 to provide evidence in support of the hypothesis that induction of prominent EADs, DADs, and triggered activity occurs in a select population of cells in ventricular myocardium. The data indicate that EADs, DADs, and triggered activity produced by digitalis and Bay K 8644 are limited to or more readily induced in the deep subepicardial cell layers of the canine ventricle (M cells). Afterdepolarization-induced triggered activity was never observed in the epicardial or endocardial layers.
Sicouri
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S
Masonic Medical Research Laboratory, Utica, New York 13504.
Antzelevitch
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C
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 / Q000502:physiology; D000818:Animals; D005117:Cardiac Complexes, Premature / Q000139:chemically induced*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004285:Dogs; D004594:Electrophysiology; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D009206:Myocardium / Q000473:pathology*; D013327:Strophanthidin / Q000031:analogs & derivatives* / Q000494:pharmacology; D013610:Tachycardia / Q000139:chemically induced*
D002316:Cardiotonic Agents; D013327:Strophanthidin; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; C004681:acetylstrophanthidin