COMPARISON OF THE EFFECTS OF CLASS-I ANTIARRHYTHMIC DRUGS, CIBENZOLINE, MEXILETINE AND FLECAINIDE, ON THE DELAYED RECTIFIER K-PIG VENTRICULAR MYOCYTES( CURRENT OF GUINEA)

The effect of class I anti-arrhythmic drugs, cibenzoline, mexiletine a nd flecainide, on the delayed rectifier potassium current (I-K) in gui nea-pig Ventricular myocytes was studied using whole cell voltage clam p techniques and under blockade of the L-type calcium current by 5 mu M nitrendipine. I-K consisted of two different current systems, as rep orted by Sanguinetti and Jurkiewicz (1990), i.e. an E4031-sensitive ra pidly activating component (I-Kr) with a strong inward-going rectifica tion property and an E4031-insensitive slowly activating component (I- Ks) with little rectification. Cibenzoline (30 mu M) decreased both I- Kr and I-Ks, while flecainide (10 and 30 mu M) decreased the I-Kr excl usively. Mexiletine (30 mu M), in contrast, affected neither I-Kr nor I-Ks. Since the inhibition of I-Kr and/or I-Ks prolongs duration of ac tion potentials and refractory periods, class I drugs which also posse ss the class III effect may have additional effects in treating certai n re-entrant arrhythmias. (C) 1996 Academic Press Limited