Blockade by antiarrhythmic drugs of glibenclamide‐sensitive K+ channels in Xenopus oocytes

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Abstract
1 The outward K+ current induced by KRN2391 (K+ channel opener) in Xenopus oocytes is blocked by glibenclamide. We have investigated the effects of various classes (I-IV) of antiarrhythmic drugs on this KRN2391-induced response. 2 All class I antiarrhythmic drugs (Na+ channel blockers) tested concentration-dependently suppressed KRN2391-induced responses with the rank order of potency (IC50 in μm), disopyramide (17.8) > aprindine (29.5) > propafenone (63.1) > ajmaline (145) > quinidine (151). Flecainide, SUN1165, lignocaine, mexiletine and procainamide were much less potent (IC50, 450– > 1000 μm) than quinidine. 3 The class II antiarrhythmic drugs (β-blockers), timolol, (−)- and (±)- propranolol, and (+)-propranolol (a non-β-blocker) inhibited KRN2391-induced K+ currents in a concentration-dependent manner with values for IC50 (μm) of 79, 131, 151 and 129, respectively, whilst butoxamine, oxprenolol, alprenolol, pindolol, nadolol, metoprolol and acebutolol were either weak (IC50, 300 μm — 600 μm) or virtually inactive (IC50, > 1000 μm). 4 The class III antiarrhythmic drugs, amiodarone and (+)-sotalol scarcely affected KRN2391 responses. 5 All class IV drugs (Ca2+ antagonists) tested suppressed KRN2391-induced responses in a concentration-dependent manner with an IC50 of 6.3 μm for bepridil, 38 μm for prenylamine, 85 μm for verapamil and 135 μm for diltiazem. 6 In conclusion, antiarrhythmic drugs of classes I, II and IV potently blocked glibenclamide-sensitive K+ channels in Xenopus oocytes.