Direct actions of cocaine on cardiac cellular electrical activity.
The hypothesis that cocaine has Class I-type antiarrhythmic drug effects was tested in tissues isolated from rabbit heart with standard microelectrode methods. Propranolol (1 microM) was used to block beta-adrenergic effects. The actions of cocaine on cellular electrophysiology were concentration- and time-dependent and were reversible. In paced right atrial (RA) and right ventricular papillary (RVP) tissues, cocaine produced a profound prolongation of the effective refractory period (ERP) assessed by either premature stimulation or minimum pacing interval. ERP was increased up to eightfold in RA tissue and doubled in RVP tissue by 60 microM cocaine. This concentration of cocaine depressed action potential phase 0 depolarization 80% in RA tissue and 53% in RVP tissue but had no effect on resting membrane potentials. Automaticity was moderately depressed in sinus node (34% decrease in rate) but not in tricuspid valve cells. Phase 0 depolarization was not altered in these spontaneously active slow-response cells. Repolarization was depressed in RA, tricuspid valve, and sinus node cells leading to a twofold increase in action potential duration during exposure to cocaine. Evidence from the effects on cellular action potentials suggests that cocaine affects both fast Na+ channels and repolarizing K+ but not Ca2+ channels. We conclude that cocaine has Class I-type activity and the effects on ERP are extreme.
Przywara
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DA
Department of Pharmacology, Wayne State University School of Medicine, Detroit, Michigan 48201.
Dambach
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GE
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002304:Cardiac Pacing, Artificial; D003042:Cocaine / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006325:Heart Atria; D008297:Male; D009206:Myocardium / Q000166:cytology*; D010210:Papillary Muscles / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D011433:Propranolol / Q000494:pharmacology; D011817:Rabbits; D012849:Sinoatrial Node / Q000166:cytology / Q000502:physiology; D014261:Tricuspid Valve / Q000166:cytology / Q000502:physiology
D011433:Propranolol; D003042:Cocaine