盐酸关附甲素对HERG基因F656C突变钾通道的影响  

Effects of acehytisine hydrochloride on the F656C mutation of HERG K+ channel

作　　者：黄兴福[1] 杨艳敏[1] 朱俊[1] 戴研[1] 浦介麟[2] 

机构地区：[1]北京协和医学院阜外心血管病医院急症抢救中心,北京100037 [2]北京协和医学院阜外心血管病医院病理生理实验中心,北京100037

出　　处：《中国新药杂志》2010年第7期612-616,共5页Chinese Journal of New Drugs

基　　金：中央级公益性科研院所基本科研业务专项(2006F002)

摘　　要：目的:评价盐酸关附甲素(AHH)对HERG基因F656C突变表达的钾通道的影响。方法:采用标准的全细胞膜片钳技术记录不同浓度的AHH对F656C突变表达的快速激活延迟整流钾电流(IKr)的影响;应用免疫蛋白印迹技术(Western blot)评价AHH对HERG钾通道蛋白的影响。结果:AHH对突变后IKr通道的峰电流(IHERG)和尾电流(Itail)具有抑制效应,并使得激活曲线左移。高浓度的AHH可抑制HERG钾通道蛋白的转运,且对F656C突变表达的HERG钾通道蛋白抑制更明显。结论:AHH主要是结合在HERG通道的S6区从而抑制钾电流。AHH不影响HERG蛋白的合成,但高浓度的AHH可抑制HERG蛋白的转运。Objective：To evaluate the electrophysiogical effects of acehytisine hydrochloride on the rapidly activating delayed rectifier potassium current （IKr） encoded by the F656C mutation of HERG gene,and on the HERG protein trafficking.Methods：The whole-cell patch clamp method was used to evaluate the effects of acehytisine hydrochloride on the IKr.Western blot analysis was used to observe the effects of acehytisine hydrochloride on the protein expression.Results：Acehytisine hydrochloride produced a concentration-dependent blockage of the IHERG and Itail.The activation curve was shifted in a negative direction by acehytisine hydrochloride.High concentration of acehytisine hydrochloride inhibited HERG K^＋ channel protein trafficking,and F656C mutation enhanced the inhibition of protein trafficking.Conclusion：Acehytisine hydrochloride inhibits HERG K^＋ channel current via S6 domain.In addtition,it does not inhibit protein synthesis but inhibits protein trafficking.

关 键 词：关附甲素 钾通道 HERG基因 免疫蛋白印迹技术 突变蛋白 

分 类 号：R96[医药卫生—药理学] R972.2[医药卫生—药学]