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钩藤碱对{sl human ether--a--go--go}相关基因通道的抑制作用

桂乐, 李之望, 杜戎, 袁国会, 李伟, 任法鑫, 李婧, 杨钧国

南通大学附属医院心内科.江苏,南通 226000；华中科技大学同济医学院神经生物学教研室.湖北,武汉 430030；华中科技大学同济医学院协和医院心血管病研究所.湖北,武汉 430030

摘要

将{sl human ether--a--go--go}相关基因(HERG)cRNA注射到非洲爪蟾卵母细胞，采用双电极电压钳技术，观察钩藤碱对表达电流的影响。结果显示：(1)钩藤碱抑制HERG通道的表达是浓度依赖性的，IC_(50)为(773.4±42.5) #mu#mol/L。(2)钩藤碱抑制HERG通道的表达是电压依赖性的，最大抑制率在--20 mV，为15%。上述结果提示，钩藤碱抑制HERG编码的钾通道，导致心室复极时间延长，揭示了与钩藤碱相关的心肌钾通道的分子生物学基础。

关键词： human ether-a-go-go相关基因; 钩藤碱; 卵母细胞; 双电极电压钳

Inhibitory effect of rhynchophylline on {sl human ether--a--go--go} related gene channel

Gui Le, Li Zhiwang, Du Rong, Yuan Guohui, Li Wei, Ren Faxin, Li Jing, Yang Junguo

Department of Cardiology, Affiliated Hospital, Nantong University.Nantong 226000,Jiangsu；China；Institute of Cardiovascular Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology.Wuhan 430030,Hubei

Abstract

We studied the effects of Chinese traditional medicine rhynchophylline (Rhy) on human ether-a-go-go related gene (HERG) channel and characterized the electrophysiological properties of Rhy's pharmacological effect on HERG channel using Xenopus oocytes. Xenopus oocytes were injected with either 23 nl (5.75 ng) HERG cRNA or 23 nl distilled water. Xenopus oocytes were randomly assigned to receive one of the following different concentrations of Rhy: (1) control, (2)10 #mu#mol/L Rhy, (3)100 #mu#mol/L Rhy, (4) 500 #mu#mol/L Rhy, (5) 1 000 #mu#mol/L Rhy, (6) 10 000 #mu#mol/L Rhy. Cell currents were recorded in oocytes. The peak tail currents of HERG channel were inhibited by Rhy. The inhibition was in a dose-dependent manner [IC_(50)=(773.4±42.5) #mu#mol/L]. Experiment with 100 #mu#mol/L Rhy indicated that the degree of HERG blockade showed some voltage dependence (within -40 mV to -20 mV ). Kinetic analyses revealed that Rhy decreased the rate of channel activation. The findings indicate that Rhy inhibits HERG encoded potassium channels. It may underline the molecular mechanism of myocardial electrophysiological characteristics associated with this drug.

Key words: HERG;rhynchophylline;oocyte;two-microelectrode voltage clamp

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引用本文：

桂乐, 李之望, 杜戎, 袁国会, 李伟, 任法鑫, 李婧, 杨钧国. 钩藤碱对{sl human ether--a--go--go}相关基因通道的抑制作用[J]. 生理学报 2005; 57 (5): .

Gui Le, Li Zhiwang, Du Rong, Yuan Guohui, Li Wei, Ren Faxin, Li Jing, Yang Junguo. Inhibitory effect of rhynchophylline on {sl human ether--a--go--go} related gene channel. Acta Physiol Sin 2005; 57 (5): (in Chinese with English abstract).