ANTIARRHYTHMIC DRUGS, CLOFILIUM AND CIBENZOLINE ARE POTENT INHIBITORS OF GLIBENCLAMIDE-SENSITIVE K+ CURRENTS IN XENOPUS-OOCYTES

1 The novel K+ channel opener, Y-26763 induced outward K+ currents in voltage-clamped follicle-enclosed Xenopus oocytes in a concentration-dependent manner with an EC50 value of 58 mum. 2 The Y-26763-induced K+ current was completely and reversibly blocked by glibenclamide (an ATP-sensitive K+ channel blocker) in a concentration-dependent manner (IC50 140 nM). Effects of several antiarrhythmic drugs on Y-26763-induced glibenclamide-sensitive K+ currents were investigated. 3 (+/-)-Cibenzoline, RS-2135, pirmenol, lorcainide and KW-3407 (class I antiarrhythmic drugs, Na+ channel blockers) suppressed Y-26763 responses in a concentration-dependent manner with IC50 values (in mum) of 6.6, 54, 68, 71 and 370, respectively. 4 Clofilium, E-4031, MS-551 and bretylium (class III antiarrhythmic drugs which increase the action potential duration) also suppressed Y-26763 responses concentration-dependently, IC50 values (in muM) were 3.3, 660, 980 and greater-than-or-equal-to 2000, respectively. N-acetylprocainamide (class III antiarrhythmic drug) scarcely suppressed Y-26763 responses. 5 The glibenclamide-sensitive K+ currents elicted by KRN2391 were also suppressed by all these antiarrhythmic drugs. 6 The antiarrhythmic drugs, clofilium and (+/-)-cibenzoline block glibenclamide-sensitive K+ channels in Xenopus oocytes at concentrations comparable to their therapeutic plasma levels.