抗心律失常药物对非洲爪蟾卵母细胞中格列本脲敏感钾通道的阻断作用。
Blockade by antiarrhythmic drugs of glibenclamide-sensitive K+ channels in Xenopus oocytes.
作者信息
Sakuta H, Okamoto K, Watanabe Y
机构信息
Department of Pharmacology, National Defense Medical College, Saitama, Japan.
出版信息
Br J Pharmacol. 1992 Dec;107(4):1061-7. doi: 10.1111/j.1476-5381.1992.tb13407.x.
Abstract
- 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 microM), 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 microM) than quinidine. 3. The class II antiarrhythmic drugs (beta-blockers), timolol, (-)- and (+/-)- propranolol, and (+)- propranolol (a non-beta-blocker) inhibited KRN2391-induced K+ currents in a concentration-dependent manner with values for IC50 (microM) of 79, 131, 151 and 129, respectively, whilst butoxamine, oxprenolol, alprenolol, pindolol, nadolol, metoprolol and acebutolol were either weak (IC50, 300 microM-600 microM) or virtually inactive (IC50, > 1000 microM). 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 microM for bepridil, 38 microM for prenylamine, 85 microM for verapamil and 135 microM for diltiazem. 6. In conclusion, antiarrhythmic drugs of classes I, II and IV potently blocked glibenclamide-sensitive K+ channels in Xenopus oocytes.
摘要
- 格列本脲可阻断非洲爪蟾卵母细胞中由KRN2391（一种钾通道开放剂）诱导产生的外向钾电流。我们研究了各类（I - IV类）抗心律失常药物对这种由KRN2391诱导的反应的影响。2. 所有测试的I类抗心律失常药物（钠通道阻滞剂）均浓度依赖性地抑制KRN2391诱导的反应，其效力顺序（IC50，单位为微摩尔）为：丙吡胺（17.8）> 阿普林定（29.5）> 普罗帕酮（63.1）> 阿吗灵（145）> 奎尼丁（151）。氟卡尼、SUN1165、利多卡因、美西律和普鲁卡因胺的效力远低于奎尼丁（IC50为450 - > 1000微摩尔）。3. II类抗心律失常药物（β受体阻滞剂）噻吗洛尔、（ - ） - 和（±） - 普萘洛尔以及（ + ） - 普萘洛尔（一种非β受体阻滞剂）均浓度依赖性地抑制KRN2391诱导的钾电流，其IC50（微摩尔）值分别为79、131、151和129，而布托洛尔、氧烯洛尔、阿普洛尔、吲哚洛尔、纳多洛尔、美托洛尔和醋丁洛尔要么作用较弱（IC50为300微摩尔 - 600微摩尔），要么几乎无活性（IC50，> 1000微摩尔）。4. III类抗心律失常药物胺碘酮和（ + ） - 索他洛尔几乎不影响KRN2391反应。5. 所有测试的IV类药物（钙拮抗剂）均浓度依赖性地抑制KRN2391诱导的反应，苄普地尔的IC50为6.3微摩尔，普尼拉明为38微摩尔，维拉帕米为85微摩尔，地尔硫䓬为135微摩尔。6. 总之，I、II和IV类抗心律失常药物可有效阻断非洲爪蟾卵母细胞中对格列本脲敏感的钾通道。
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