State-dependent blockade of human ether-a-go-go-related gene (hERG) K~+ channels by changrolin in stably transfected HEK293 cells

	State-dependent blockade of human ether-a-go-go-related gene (hERG) K~+ channels by changrolin in stably transfected HEK293 cells
	Chen Weihai; Wang Wenyi; Zhang Jie; Yang Ding; Wang Yiping
刊名	Acta Pharmacologica Sinica
	2010
卷号	31 期号:8 页码:915
关键词	TORSADES-DE-POINTES POTASSIUM CHANNELS PROLONGATION DERIVATIVES BINDING DRUGS
ISSN号	1671-4083
英文摘要	Aim: To study the effect of changrolin on the K + channels encoded by the human ether-a-go-go -related gene (hERG). Methods: hERG channels were heterologously stably expressed in human embryonic kidney 293 cells, and the hERG K + currents were recorded using a standard whole-cell patch-clamp technique. Results: Changrolin inhibited hERG channels in a concentration-dependent and reversible manner (IC 50 =18.23 μmol P <0.01, n =9) but did not significantly affect the steady-state inactivation of hERG ( n =5, P >0.05). The relative block of hERG channels by changrolin was close to zero at the time point of channel opening by the depolarizing voltage step and quickly increased afterwards. The maximal block was achieved in the inactivated state, with no further development of the open channel block. In the “envelope of tails” experiments, the time constants of activation were found to be 287.8±46.2 ms and 174.2±18.4 ms, respectively, for the absence and presence of 30 μmol P <0.05, n =7). The onset of inactivation was accelerated significantly by changrolin between ?40 mV and +60 mV ( P <0.05, n =7). Conclusion: The results demonstrate that changrolin is a potent hERG blocker that preferentially binds to hERG channels in the open and inactivated states.
语种	英语
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/285278]
专题	中国科学院上海药物研究所
作者单位	中国科学院上海药物研究所
推荐引用方式 GB/T 7714	Chen Weihai,Wang Wenyi,Zhang Jie,et al. State-dependent blockade of human ether-a-go-go-related gene (hERG) K~+ channels by changrolin in stably transfected HEK293 cells[J]. Acta Pharmacologica Sinica,2010,31(8):915.
APA	Chen Weihai,Wang Wenyi,Zhang Jie,Yang Ding,&Wang Yiping.(2010).State-dependent blockade of human ether-a-go-go-related gene (hERG) K~+ channels by changrolin in stably transfected HEK293 cells.Acta Pharmacologica Sinica,31(8),915.
MLA	Chen Weihai,et al."State-dependent blockade of human ether-a-go-go-related gene (hERG) K~+ channels by changrolin in stably transfected HEK293 cells".Acta Pharmacologica Sinica 31.8(2010):915.