[1]韩圣娜),刘 备),孔 岚),等.依托咪酯对HEK-293细胞中异源表达的hERG钾通道电流的抑制作用*[J].郑州大学学报(医学版),2016,(02):204-208.
 HAN Shengna),LIU Bei),KONG Lan),et al.Inhibition effects of etomidate on hERG K+ channel expressed in HEK-293 cells[J].JOURNAL OF ZHENGZHOU UNIVERSITY(MEDICAL SCIENCES),2016,(02):204-208.
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依托咪酯对HEK-293细胞中异源表达的hERG钾通道电流的抑制作用*()
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《郑州大学学报(医学版)》[ISSN:1671-6825/CN:41-1340/R]

卷:
期数:
2016年02期
页码:
204-208
栏目:
应用研究
出版日期:
2016-03-20

文章信息/Info

Title:
Inhibition effects of etomidate on hERG K+ channel expressed in HEK-293 cells
作者:
韩圣娜1)刘 备1)孔 岚2)李 靓1)冯 馨1)张 卫3)张莉蓉1)#
1)郑州大学基础医学院药理学教研室 郑州 450001
2)河南省肿瘤医院麻醉科 郑州 450008
3)郑州大学第一附属医院麻醉科 郑州 450052
Author(s):
HAN Shengna1)LIU Bei1)KONG Lan2)LI Liang1)FENG Xin1)ZHANG Wei3)ZHANG Lirong1)
1)Department of Pharmacology, College of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001
2)Department of Anesthesiology,Henan Cancer Hospital, Zhengzhou 450008
3)Department of Anesthesiology, the First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052
关键词:
依托咪酯 hERG钾通道 全细胞膜片钳 HEK-293细胞
Keywords:
etomidate hERG K+ channel whole-cell patch clamp HEK-293 cell
分类号:
R322.1; R978.1
摘要:
目的:观察依托咪酯对HEK-293细胞中异源表达的hERG钾通道电流的抑制作用及其机制。方法:采用脂质体瞬时转染的方法将野生型hERG(WT-hERG)、突变型Y652A-hERG和F656C-hERG分别转染人胚胎肾细胞HEK-293,应用全细胞膜片钳技术记录依托咪酯对转染后HEK-293细胞表达的hERG钾通道电流的抑制作用以及对激活曲线和失活曲线的影响。结果:依托咪酯可浓度依赖性地抑制WT-hERG转染的HEK-293细胞钾通道电流,其半数最大抑制浓度为(6.41±2.43)μmol/L,对激活曲线和失活曲线无明显影响。与WT-hERG转染的HEK-293细胞相比,依托咪酯对突变体Y652A-hERG及F656C-hERG转染的HEK-293细胞内钾通道电流的抑制作用减弱。结论:F656C可能是依托咪酯抑制hERG钾通道的重要靶点。
Abstract:
Aim: To investigate the molecular mechanisms of etomidate on hERG K+ channel expressed in human embryonic kidney(HEK-293)cells.Methods: HEK-293 cells were transfected transiently with different hERG plasmid(WT, mutant Y652A and F656C, respectively)using lipofection. Whole-cell patch clamp technique was used to record the effects of etomidate on hERG K+ channel current,and the activation and inactivation curves expressed in HEK-293 cells.Results: Etomidate directly inhibited WT-hERG K+ current in a concentration-dependent manner, and half-maximum block concentration was(6.41±2.43)μmol/L. But etomidate did not markedly modify the activation and inactivation curves of WT-hERG K+ channel. The inhibition effects of etomidate on mutant Y652A-hERG and F656C-hERG K+ channel were attenuated compared with WT-hERG K+ channel.Conclusion: F656C may be the key target that etomidate inhibits the hERG K+ channel.

参考文献/References:

[1] CUNEO BF.The beginnings of long QT syndrome[J].Curr Opin Cardiol,2015,30(1):112
[2] MICHELS G,KOCHANEK M,PFISTER R.Life-threatening cardiac arrhythmias due to drug-induced QT prolongation:a retrospective study over 6 years from a medical intensive care unit[J].Med Klin Intensivmed Notfmed,2015.[Epub ahead of print]
[3] 朱惠敏.获得性Q-T间期延长综合症患者的麻醉观察[J].中国农村卫生事业管理,2010,30(10):885
[4] 王亚辉,王家和,尹大光.静脉麻醉药对QT间期的影响[J].临床麻醉学杂志,1996,12(3):137
[5] ERDIL F,DEMIRBILEK S,BEGEC Z,et al.Effects of propofol or etomidate on QT interval during electroconvulsive therapy[J].J ECT,2009,25(3):174
[6] PASSOT S,SERVIN F,PASCAL J,et al.A comparison of target- and manually controlled infusion propofol and etomidate/desflurane anesthesia in elderly patients undergoing hip fracture surgery[J].Anesth Analg,2005,100(5):1338
[7] 马新方,韩圣娜,张雨,等.罗红霉素对转染HERG基因人胚肾上皮细胞HERG钾通道的抑制作用[J].郑州大学学报(医学版),2010,45(5):763

备注/Memo

备注/Memo:
*国家自然科学基金青年基金项目 81200138
#通信作者,女,1964年10月生,博士,教授,研究方向:药物不良反应,E-mail:zhanglirongzzu@126.com
更新日期/Last Update: 2016-03-20