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 microM. 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 microM) 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 microM) were 3.3, 660, 980 and > or = 2000, respectively. N-acetylprocainamide (class III antiarrhythmic drug) scarcely suppressed Y-26763 responses. 5. The glibenclamide-sensitive K+ currents elicited 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.
Sakuta
H
H
Department of Pharmacology, National Defense Medical College, Saitama, Japan.
Okamoto
K
K
Watanabe
Y
Y
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D000959:Antihypertensive Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology; D001578:Benzopyrans / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004594:Electrophysiology; D005260:Female; D005905:Glyburide / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects*; D011725:Pyridines / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology*; D014982:Xenopus laevis
D000889:Anti-Arrhythmia Agents; D000959:Antihypertensive Agents; D001578:Benzopyrans; D007093:Imidazoles; D015221:Potassium Channels; D011725:Pyridines; D000644:Quaternary Ammonium Compounds; C070492:N-cyano-N'-(2-nitroxyethyl)-3-pyridinecarboximidamide methanesulfonate; C022799:clofilium; C074338:Y 26763; D005905:Glyburide; C032151:cifenline