Hexachlorophene Is a Potent KCNQ1/KCNE1 Potassium Channel Activator Which Rescues LQTs Mutants
文献类型：期刊论文
| 作者 | Zheng, Yueming3; Zhu, Xuejing3; Zhou, Pingzheng3; Lan, Xi3; Xu, Haiyan3; Li, Min1,2,3; Gao, Zhaobing3
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| 刊名 | PLOS ONE
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| 出版日期 | 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. |
| WOS关键词 | LONG-QT-SYNDROME ; I-KS ; PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE ; KV7 CHANNELS ; MUTATIONS ; KVLQT1 ; ISK ; KCNQ1 ; ARRHYTHMIAS ; MECHANISMS |
| 资助项目 | National Natural Science Foundation of China (NSFC)[81072579] ; NIH[MH084691] ; NIH[GM070959] |
| WOS研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| WOS记录号 | WOS:000313236200168 |
| 出版者 | PUBLIC LIBRARY SCIENCE |
| 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). |
入库方式： OAI收割
来源：上海药物研究所
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