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IQ23对豚鼠心室肌细胞复极和延迟整流钾电流两种成分的作用

李新华, 阎升, 姚伟星, 夏国瑾, 江明性, 黄文龙, 彭司勋   

  1. 1. 同济医科大学基础医学院药理教研室, 武汉 430030
    2. 中国药科大学药物化学研究室, 南京 210009
  • 收稿日期:1997-11-09 修回日期:1998-03-09 出版日期:1999-03-15 发布日期:1999-03-15

Effects of IQ23 on the Repolarization and Both Components of the Delayed Rectifier Potassium Current in Guinea Pig Ventricular Myocytcs

Li Xinhua, Yan Sheng, Yao Weixing, Xia Guojin, Jiang Mingxing, Huang Wenlong, Peng Sixun   

  1. 1.Department of Pharmacology, Tongji Medical University, Wuhan 430030
    2.Division of Medical Chemistry, China Pharmaceutical University, Nanjing 210009
  • Received:1997-11-09 Revised:1998-03-09 Online:1999-03-15 Published:1999-03-15

摘要: 采用膜片钳全细胞记录技术, 研究了具有抗心律失常作用的苄基异喹啉衍化物IQ23对豚鼠心室肌单细胞动作电位(AP)和钾电流的作用。结果表明: IQ2310, 30, 100 μmol·L-1呈浓度依赖性的减慢AP复极, APD90分别延长15%, 28%31%, 此效应不依赖细胞外Ca2+。电压钳制下记录延迟整流钾电流, IQ23对其两种成分, IksIkr, 都有阻断作用, 30100 mol·L-1 IQ23阻断Iks21%26%, Ikr67%86%。即使在100 mol·L-1, IQ23也不影响内向整流钾电流(Ikl)。本实验表明, IQ23能浓度依赖性的延长心室肌细胞动作电位时程(APD), 此效应与胞外Ca2+无关。IQ23IksIkr两种成分都有阻断作用, 无明显的选择性。

关键词: IQ23, 抗心律失常药, 膜片钳, 动作电位, 钾通道, 心室肌细胞, 豚鼠

Abstract: Using patch clamp whole cell recording techiques, we examined the effects of IQ23, a benzyl-isoquinoline derivative with antiarrhythmic activities, on the action potential (AP) and potassium currents in single guinea pig ventricular myocytes. The results showed that IQ23 at 10, 30and 100 μmol·L-1 slowed the repolarization in AP dose-dependently. The APD90 were prolonged by15%, 28% and 31% respectively. This effect did not depend on the extracellular Ca2+. In voltage clamp mode, IQ23 effectively blocked both the components of the delayed rectifier potassium current (Ik), i.e., Iks and Ikr. At concentrations of 30 and 100 μmol·L-1, IQ23 suppressed Iks by 21% and 26% and suppressed Ikr by 67% and 86% respectively. But even at 100 μmol·L-1, IQ23 had little effect onthe inward rectifier potassium current (Ikl). It is concluded: (1) IQ23 can dose-dependently prolong APD in the ventriculas myocytes of guinea pig, the effect does not depend on the extracellular Ca2+; (2) IQ23 blocks both Iks and Ikr in the ventricular myocytes without obvious specificities between them.

Key words: IQ13, Antiarrhythmic drug, Patch clamp technic, Action potential, Potassiumchannel, Ventricular myocyte, Guinea pig

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