Manual whole-cell patch-clamping of the HERG cardiac K+ channel.
Delayed ventricular repolarization, as measured by a prolongation of the QT interval on the electrocardiogram, is a major safety issue in the drug development process. It is now recognized that most cases of drug-induced QT prolongation arise from direct pharmacological inhibition of the human ether-a-go-go-related gene (HERG) cardiac K+ channel. It is standard practice to test a drug's ability to interact with the HERG channel prior to entry into clinical trials. This testing is used, as part of a larger battery of tests, to help predict the cardiac safety profile of a drug. Manual whole-cell patch-clamping provides the most sensitive and accurate way to examine the biophysical and pharmacological properties of the HERG cardiac K+ channel.
Disposition, Safety and Animal Research, Sanofi-Aventis R&D, Bridgewater, NJ, USA.
Xiao-Liang
XL
Chen
Jiesheng
J
Kang
David
D
Rampe
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D000072237:ERG1 Potassium Channel; D055724:Electrophysiological Phenomena; D051638:Ether-A-Go-Go Potassium Channels / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism*; D018408:Patch-Clamp Techniques / Q000379:methods*
D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human