Chen Xiao-Liang, Kang Jiesheng, Rampe David
Disposition, Safety and Animal Research, Sanofi-Aventis R&D, Bridgewater, NJ, USA.
Methods Mol Biol. 2011;691:151-63. doi: 10.1007/978-1-60761-849-2_9.
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.
通过心电图上QT间期延长来衡量的心室复极延迟，是药物研发过程中的一个主要安全问题。现在人们认识到，大多数药物引起的QT间期延长病例是由于直接药理抑制人醚-à- go-go相关基因（HERG）心脏钾通道所致。在进入临床试验之前测试药物与HERG通道相互作用的能力是标准做法。作为一系列更广泛测试的一部分，这种测试用于帮助预测药物的心脏安全性。手动全细胞膜片钳技术提供了检查HERG心脏钾通道生物物理和药理特性的最灵敏和准确的方法。
