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应用膜片钳技术检测药物对HERG通道抑制作用的实验过程及要点 被引量:2

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摘要 目的应用膜片钳技术检测药物对人类ether-a-go-go相关基因(human ether-a-go-go-related gene,HERG)编码的钾离子通道的作用。探讨离子电流记录过程及实验要点。方法选择稳定转染并表达人源心肌HERG离子通道的HEK293细胞,通过全细胞记录方式,记录HERG电流。结果成功记录到HERG步阶电流和尾电流,步阶电流的Ⅰ-Ⅴ曲线表现为特征性的倒钟形结构,尾电流在去极化时迅速上升,在+10 m V时接近峰值。阳性药物E-4031能明显阻断HERG电流。检测的化合物A对HERG电流具有抑制效应,半数抑制浓度IC50为109μmol/L。结论体外HERG实验可直接检测药物对HERG电流的抑制作用,膜片钳的正确操作及电流记录是实验成败的关键因素。
作者 夏静 彭双清
出处 《军事医学》 CAS CSCD 北大核心 2015年第11期884-886,共3页 Military Medical Sciences
基金 国家科技重大专项资助项目(2009ZX09501-034)
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参考文献11

  • 1李波.安全药理学的国内外发展概况[J].中国新药杂志,2004,13(11):964-968. 被引量:8
  • 2国家食品药品监督管理总局.关于发布药物安全药理学研究技术指导原则等8项技术指导原则的通告(第4号).北京:CFDA,2014.http://www.sda.gov.cn/WS0l/C10087.100983.html.
  • 3赵杰,郑建全.HERG编码的钾离子通道与新药评价[J].军事医学科学院院刊,2005,29(4):386-389. 被引量:4
  • 4Perrin M J, Subbiah RN, Vandenberg JI, et al. Human ether-a- go-go related gene (hERG) K channels: function and dysfunc- tion [J]. Prog Biophys Mol Biol, 2008, 98(2 -3) :137 - 148.
  • 5Han S, Zhang Y, Chen Q, et al. Fluconazole inhibits hERG K channel by direct block and disruption of protein trafficking [ J]. Eur J Pharmacol, 2011,650 ( 1 ) : 138 - 44.
  • 6Choi SH, Shin TJ, Hwang SH, et al. Ginsenoside Rg3 deceler- ates hERG K channel deactivation through Set631 residue inter- action [J]. Eur J Pharmacol, 2011, 663(1-3) :59-67.
  • 7孙洪良,魏晓丽,华南,闫海涛,张树卓,刘晓燕,郑建全.爪蟾卵母细胞表达hERG1b钾通道的电生理学特性研究[J].军事医学,2011,35(3):184-188. 被引量:2
  • 8Witchel HJ, Milnes JT, Mitcheson JS, et al. Troubleshooting problems with in vitro screening of drugs for QT interval prolonga- tion using HERG K + channels expressed in mammalian cell lines and Xenopus oocytes [ J ]. J Pharmacol Toxicol Methods, 2002, 48(2) :65 -80.
  • 9Yao JA, Du X, Lu D, et al. Estimation of potency of HERG channel blockers: impact of voltage protocol and temperature [ J ]. J Pharmaeol Toxicol Methods, 2005, 52 ( 1 ) : 146 - 53.
  • 10Webster R, Leishman D, Walker D. Towards a drug concentra- tion effect relationship for QT prolongation and torsades de pointes [J]. Curr Ooin Drug Discov Dev. 2002: 5(1) ,116 -126.

二级参考文献26

  • 1[1]ICH S7A.Safety pharmacology studies for human pharmaceuticals[EB/OL].http://www.fda.gov/cder/guidance/index.htm,2001-07-15.
  • 2[2]ICH S7B.Safety pharmacology studies for assessing the potential for delayed ventricular repolarization (QT interval prolongation) by human pharmaceuticals[EB/OL].http://www.fda.gov./cder/guidance/index.htm,2002-06-12.
  • 3[3]Murphy DJ.Safety pharmacology of the respiratory system:techniques and study design[J].Drug Dev Res,1994,32:237-246.
  • 4De Ponti F,Poluzzi E, Montanaro N. QT interval prolongation by non-cardiac drugs: lessons to be learned from recent experience[J]. Eur J Clin Pharmacol, 2000, 56(1): 1-18.
  • 5Tamargo J. Drug-induced torsade de pointes: from molecular biology to bedside[J]. Jpn J Pharmacol, 2000, 83(1): 1-19.
  • 6Petersen CI, McFarland TR, Stepanovic SZ, et al.In vivo identification of genes that modify ether-α-go-go-related gene activity in Caenorhabditis elegans may also affect human cardiac arrhythmia[J]. Proc Natl Acad Sci USA, 2004, 101(32):11773-11778.
  • 7Warmke JW, Ganetzky B. A family of potassium channel genes related to eag in Drosophila and mammals[J]. Proc Natl Acad Sci USA, 1994, 91(8): 3438-344.
  • 8Jiang C, Atkinson D, Towbin JA, et al. Two long QT syndrome loci map to chromosomes 3 and 7 with evidence for further heterogeneity[J]. Nat Genet,1994, 8(2): 141.
  • 9Abbott GW, Sesti F, Splawski I, et al.MiRP1 forms Ikr potassium channels with HERG and is associated with cardiac arrhythmia[J]. Cell, 1999, 97(2): 175.
  • 10FU EY, Clemo HF, Ellen Bogen KA. Acquired QT prolongation: mechanism and implication[J]. Cardiol Rev,1998, 6(6): 319-324.

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