抗心律失常药物氯非铵和西苯唑啉是非洲爪蟾卵母细胞中格列本脲敏感钾电流的强效抑制剂。

Antiarrhythmic drugs, clofilium and cibenzoline are potent inhibitors of glibenclamide-sensitive K+ currents in Xenopus oocytes.

Sakuta H, Okamoto K, Watanabe Y

Department of Pharmacology, National Defense Medical College, Saitama, Japan.

Br J Pharmacol. 1993 Jul;109(3):866-72. doi: 10.1111/j.1476-5381.1993.tb13655.x.

Abstract

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.

摘要

新型钾通道开放剂Y-26763能以浓度依赖的方式在电压钳制的非洲爪蟾卵泡包裹卵母细胞中诱导外向钾电流，其半数有效浓度（EC50）值为58微摩尔。2. Y-26763诱导的钾电流被格列本脲（一种ATP敏感性钾通道阻滞剂）以浓度依赖的方式完全且可逆地阻断（半数抑制浓度[IC50]为140纳摩尔）。研究了几种抗心律失常药物对Y-26763诱导的格列本脲敏感性钾电流的影响。3. （±）-西苯唑啉、RS-2135、吡美诺、劳卡尼和KW-3407（I类抗心律失常药物，钠通道阻滞剂）以浓度依赖的方式抑制Y-26763反应，其IC50值（以微摩尔计）分别为6.6、54、68、71和370。4. 氯非铵、E-4031、MS-551和溴苄铵（能延长动作电位时程的III类抗心律失常药物）也以浓度依赖的方式抑制Y-26763反应，IC50值（以微摩尔计）分别为3.3、660、980和≥2000。N-乙酰普鲁卡因胺（III类抗心律失常药物）几乎不抑制Y-26763反应。5. KRN2391引发的格列本脲敏感性钾电流也被所有这些抗心律失常药物抑制。6. 抗心律失常药物氯非铵和（±）-西苯唑啉在非洲爪蟾卵母细胞中以与其治疗血浆水平相当的浓度阻断格列本脲敏感性钾通道。