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ABOLITION OF DRUG‐INDUCED EARLY AFTERDEPOLARIZATIONS BY POTASSIUM CHANNEL ACTIVATORS IN GUINEA‐PIG PURKINJE FIBRES
Author(s) -
Brosch SF,
Studenik C,
Heistracher P
Publication year - 1998
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1998.t01-11-.x
Subject(s) - afterdepolarization , pinacidil , disopyramide , nicorandil , purkinje fibers , chemistry , cromakalim , sotalol , torsades de pointes , guinea pig , pharmacology , quinidine , medicine , potassium channel , channel blocker , glibenclamide , endocrinology , qt interval , electrophysiology , calcium , atrial fibrillation , repolarization , diabetes mellitus
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 μmol/L could be completely abolished by nicorandil at concentrations between 50 and 500 μmol/L. The extracellular K + concentration was 2.7 mmol/L. 3. Disopyramide‐induced EAD at concentrations of 10, 20 and 30 μmol/L in a Tyrode’s solution containing 1.35 mmol/L K + and these EAD were abolished by pinacidil (30 and 100 μmol/L) and lemakalim (10 and 30 μmol/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.