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标题：HERG K+ Channel Blockade by the Novel Antiviral Drug Sophocarpine
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作者：Xue-Ling Zhao ; Zhi-Ping Qi ; Cheng Fang 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2008
卷号：31
期号：4
页码：627-632
DOI：10.1248/bpb.31.627
出版社：The Pharmaceutical Society of Japan
摘要：Human ether-à-go-go-related gene (HERG) encodes the rapid component of the cardiac delayed rectifier K⁺ current, which has an important role in the repolarization of the cardiac action potential. QT interval prolongation through HERG channel inhibition is associated with a risk of torsade de pointes arrhythmias and is a major challenge for drug development. The effects of the novel antiviral drug sophocarpine (SC) were examined on stably expressed HERG channels in human embryonic kidney (HEK293) cells using a whole-cell patch clamp technique, Western blot analysis and immunofluorescence experiments. SC inhibited HERG channels in a concentration-dependent manner, with an IC₅₀ of 100—300 μ M . SC significantly accelerated channel inactivation, recovery from inactivation and onset of inactivation. In addition, it had no effect on channel activation and deactivation. Based on Western blot and immunofluorescence results, SC had no significant effect on the expression of HERG protein. In summary, SC is a potent blocker of HERG K⁺ channels that functions by changing the channel inactivation kinetics. In addition, SC has no effect on the generation and trafficking of HERG protein.
关键词：sophocarpine;human ether-à-go-go-related gene;patch clamp;Western blot;immunofluorescence;human embryonic kidney cell