Isoform-specific prolongation of Kv7 (KCNQ) potassium channel opening mediated by new molecular determinants for drug-channel interactions
文献类型：期刊论文
| 作者 | Gao, Zhaobing4,6 ; Zhang, Tangzhi5; Wu, Meng6; Xiong, Qiaojie3,6; Sun, Haiyan2,6; Zhang, Yinan5; Zu, Liansuo5; Wang, Wei1,5; Li, Min6
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| 刊名 | Journal of Biological Chemistry
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| 出版日期 | 2010-09-03 |
| 卷号 | 285期号:36页码:28322-28332 |
| ISSN号 | 00219258 |
| DOI | 10.1074/jbc.M110.116392 |
| 文献子类 | Article |
| 英文摘要 | Kv7 channels, especially Kv7.2 (KCNQ2) and Kv7.3 (KCNQ3), are key determinants for membrane excitability in the brain. Some chemical modulators of KCNQ channels are in development for use as anti-epileptic drugs, such as retigabine (D-23129, N-(2-amino-4-(4-fluorobenzylamino)-phenyl)), which was recently approved for clinical use. In addition, several other compounds were also reported to potentiate activity of the Kv7 channels. It is therefore of interest to investigate compound-channel interactions, so that more insights may be gained to aid future development of therapeutics. We have conducted a screen of 20,000 compounds for KCNQ2 potentiators using rubidium flux combined with atomic absorption spectrometry. Here, we report the characterization of a series of new structures that display isoform specificity and induce a marked reduction of deactivation distinct from that of retigabine. Furthermore, KCNQ2(W236L), a previously reported mutation that abolishes sensitivity to retigabine, remains fully sensitive to these compounds. This result, together with mutagenesis and other studies, suggests that the reported compounds confer a unique mode of action and involve new molecular determinants on the channel protein, consistent with the idea of recognizing a new site on channel protein. |
| 语种 | 英语 |
| 出版者 | American Society for Biochemistry and Molecular Biology Inc., 9650 Rockville Pike, Bethesda, MD 20814, United States |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/266995]  |
| 专题 | 神经药理学研究国际科学家工作站 |
| 通讯作者 | Wang, Wei |
| 作者单位 | 1.Dept. of Neuroscience, Johns Hopkins University School of Medicine, BRB311, 733 N. Broadway, Baltimore, MD 21205, United States 2.Corning Inc., 1 Science Center Rd., Corning, NY 14831, United States; 3.Cold Spring Harbor Laboratory, 1 Bungtown Rd., Cold Spring Harbor, NY 11724, United States; 4.Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 201203, China; 5.Department of Chemistry and Chemical Biology, University of New Mexico, Albuquerque, NM 87131, United States; 6.Department of Neuroscience, School of Medicine, Johns Hopkins University, Baltimore, MA 21205, United States; |
| 推荐引用方式 GB/T 7714 | Gao, Zhaobing,Zhang, Tangzhi,Wu, Meng,et al. Isoform-specific prolongation of Kv7 (KCNQ) potassium channel opening mediated by new molecular determinants for drug-channel interactions[J]. Journal of Biological Chemistry,2010,285(36):28322-28332. |
| APA | Gao, Zhaobing.,Zhang, Tangzhi.,Wu, Meng.,Xiong, Qiaojie.,Sun, Haiyan.,...&Li, Min.(2010).Isoform-specific prolongation of Kv7 (KCNQ) potassium channel opening mediated by new molecular determinants for drug-channel interactions.Journal of Biological Chemistry,285(36),28322-28332. |
| MLA | Gao, Zhaobing,et al."Isoform-specific prolongation of Kv7 (KCNQ) potassium channel opening mediated by new molecular determinants for drug-channel interactions".Journal of Biological Chemistry 285.36(2010):28322-28332. |
入库方式： OAI收割
来源：上海药物研究所
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