Hexachlorophene Is a Potent KCNQ1/KCNE1 Potassium Channel Activator Which Rescues LQTs Mutants

doi:10.1371/journal.pone.0051820

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	Hexachlorophene Is a Potent KCNQ1/KCNE1 Potassium Channel Activator Which Rescues LQTs Mutants
	Zheng, Yueming 3; Zhu, Xuejing 3; Zhou, Pingzheng 3; Lan, Xi 3; Xu, Haiyan 3; Li, Min 1,2,3; Gao, Zhaobing3
刊名	PLOS ONE
	2012-12-12
卷号	7 期号:12
ISSN号	1932-6203
DOI	10.1371/journal.pone.0051820
文献子类	Article
英文摘要	The voltage-gated KCNQ1 potassium channel is expressed in cardiac tissues, and coassembly of KCNQ1 with an auxiliary KCNE1 subunit mediates a slowly activating current that accelerates the repolarization of action potential in cardiomyocytes. Mutations of KCNQ1 genes that result in reduction or loss of channel activity cause prolongation of repolarization during action potential, thereby causing long QT syndrome (LQTs). Small molecule activators of KCNQ1/KCNE1 are useful both for understanding the mechanism of the complex activity and for developing therapeutics for LQTs. In this study we report that hexachlorophene (HCP), the active component of the topical anti-infective prescription drug pHisoHex, is a KCNQ1/KCNE1 activator. HCP potently increases the current amplitude of KCNQ1/KCNE1 expressed by stabilizing the channel in an open state with an EC50 of 4.61 +/- 1.29 mu M. Further studies in cardiomyocytes showed that HCP significantly shortens the action potential duration at 1 mu M. In addition, HCP is capable of rescuing the loss of function of the LQTs mutants caused by either impaired activation gating or phosphatidylinositol-4,5-bisphosphate (PIP2) binding affinity. Our results indicate HCP is a novel KCNQ1/KCNE1 activator and may be a useful tool compound for the development of LQTs therapeutics.
资助项目	National Natural Science Foundation of China (NSFC)[81072579] ; NIH[MH084691] ; NIH[GM070959]
WOS关键词	LONG-QT-SYNDROME ; I-KS ; PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE ; KV7 CHANNELS ; MUTATIONS ; KVLQT1 ; ISK ; KCNQ1 ; ARRHYTHMIAS ; MECHANISMS
WOS研究方向	Science & Technology - Other Topics
语种	英语
出版者	PUBLIC LIBRARY SCIENCE
WOS记录号	WOS:000313236200168
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/277847]
专题	神经药理学研究国际科学家工作站
通讯作者	Li, Min
作者单位	1.Johns Hopkins Univ, Sch Med, Johns Hopkins Ion Channel Ctr, Baltimore, MD USA 2.Johns Hopkins Univ, Dept Neurosci, High Throughput Biol Ctr, Baltimore, MD USA; 3.Chinese Acad Sci, Shanghai Inst Mat Med, Key Lab Receptor Res, Shanghai 200031, Peoples R China;
推荐引用方式 GB/T 7714	Zheng, Yueming,Zhu, Xuejing,Zhou, Pingzheng,et al. Hexachlorophene Is a Potent KCNQ1/KCNE1 Potassium Channel Activator Which Rescues LQTs Mutants[J]. PLOS ONE,2012,7(12).
APA	Zheng, Yueming.,Zhu, Xuejing.,Zhou, Pingzheng.,Lan, Xi.,Xu, Haiyan.,...&Gao, Zhaobing.(2012).Hexachlorophene Is a Potent KCNQ1/KCNE1 Potassium Channel Activator Which Rescues LQTs Mutants.PLOS ONE,7(12).
MLA	Zheng, Yueming,et al."Hexachlorophene Is a Potent KCNQ1/KCNE1 Potassium Channel Activator Which Rescues LQTs Mutants".PLOS ONE 7.12(2012).