Abolition of drug-induced early afterdepolarizations by potassium channel activators in guinea-pig Purkinje fibres.
1. Drug-induced early afterdepolarizations (EAD) are considered to be the underlying mechanism of the polymorphic ventricular dysrhythmia torsades de pointes. Sotalol and disopyramide are well known to generate EAD. Therefore, it was of interest to study the effects of potassium channel activators, such as nicorandil, pinacidil and lemakalim, on those drug-induced EAD in spontaneously beating guinea-pig Purkinje fibres using the intracellular microelectrode technique. 2. Early afterdepolarizations induced by sotalol at concentrations of 80 and 160 micromol/L could be completely abolished by nicorandil at concentrations between 50 and 500 micromol/L. The extracellular K+ concentration was 2.7 mmol/L. 3. Disopyramide-induced EAD at concentrations of 10, 20 and 30 micromol/L in a Tyrode's solution containing 1.35 mmol/L K+ and these EAD were abolished by pinacidil (30 and 100 micromol/L) and lemakalim (10 and 30 micromol/L). 4. Early afterdepolarizations could be regenerated by superfusion of Purkinje fibres with K+ channel activator-free Tyrode's solution containing either sotalol or disopyramide. 5. Our results demonstrate that drug-induced EAD can be abolished by K+ channel activators and, therefore, may provide anti-arrhythmic effects in heart diseases.
Brosch
S F
SF
Institute of Pharmacology and Toxicology, University of Vienna, Austria.
Studenik
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Heistracher
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D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D019806:Cromakalim / Q000494:pharmacology / Q000627:therapeutic use; D004206:Disopyramide; D005260:Female; D006146:Guanidines / Q000494:pharmacology / Q000627:therapeutic use; D006168:Guinea Pigs; D008297:Male; D009536:Niacinamide / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D020108:Nicorandil; D020110:Pinacidil; D015221:Potassium Channels / Q000187:drug effects; D011690:Purkinje Fibers / Q000187:drug effects* / Q000502:physiology; D013015:Sotalol; D016171:Torsades de Pointes / Q000139:chemically induced / Q000188:drug therapy*
D000889:Anti-Arrhythmia Agents; D006146:Guanidines; D015221:Potassium Channels; D019806:Cromakalim; D009536:Niacinamide; D020108:Nicorandil; D020110:Pinacidil; D013015:Sotalol; D004206:Disopyramide