ABOLITION OF DRUG-INDUCED EARLY AFTERDEPOLARIZATIONS BY POTASSIUM CHANNEL ACTIVATORS IN GUINEA-PIG PURKINJE-FIBERS

1. Drug-induced early afterdepolarizations (EAD) are considered to be the underlying mechanism of the polymorphic ventricular dysrhythmia To rsades 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 th ose drug-induced EAD in spontaneously beating guinea-pig Purkinje fibr es using the intracellular microelectrode technique, 2. Early afterdep olarizations induced by sotalol at concentrations of 80 and 160 mu mol /L could be completely abolished by nicorandil at concentrations betwe en 50 and 500 mu mol/L. The extracellular K+ concentration was 2.7 mmo l/L, 3. Disopyramide-induced EAD at concentrations of 10, 20 and 30 mu mol/L in a Tyrode's solution containing 1.35 mmol/L K+ and these EAD were abolished by pinacidil (30 and 100 mu mol/L) and lemakalim (10 an d 30 mu mol/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 de monstrate that drug-induced EAD can be abolished by K+ channel activat ors and, therefore, may provide anti-arrhythmic effects in heart disea ses.