Comparison of the Effects of Class I Anti-arrhythmic Drugs, Cibenzoline, Mexiletine and Flecainide, on the Delayed Rectifier K+Current of Guinea-pig Ventricular Myocytes

The effect of class I anti-arrhythmic drugs, cibenzoline, mexiletine and flecainide, on the delayed rectifier potassium current (IK) in guinea-pig ventricular myocytes was studied using whole cell voltage clamp techniques and under blockade of the -type calcium current by 5μ nitrendipine. IKconsisted of two different current systems, as reported by Sanguinetti and Jurkiewicz (1990), i.e. an E4031-sensitive rapidly activating component (IKr) with a strong inward-going rectification property and an E4031-insensitive slowly activating component (IKs) with little rectification. Cibenzoline (30μ ) decreased both IKrand IKs, while flecainide (10 and 30μ ) decreased the IKrexclusively. Mexiletine (30μ ), in contrast, affected neither IKrnor IKs. Since the inhibition of IKrand/or IKsprolongs duration of action potentials and refractory periods, class I drugs which also possess the class III effect may have additional effects in treating certain re-entrant arrhythmias.