Discovery of talatisamine as a novel specific blocker for the delayed rectifier K+ channels in rat hippocampal neurons
文献类型：期刊论文
| 作者 | Song, M. -K.1,2; Liu, H.1 ; Jiang, H. -L.1; Yue, J. M.1; Hu, G. -Y.1; Chen, H. -Z.2
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| 刊名 | NEUROSCIENCE
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| 出版日期 | 2008-08-13 |
| 卷号 | 155期号:2页码:469-475 |
| 关键词 | talatisamine channel blocker delayed rectifier K+ channel virtual screening Aconitum alkaloids |
| ISSN号 | 0306-4522 |
| DOI | 10.1016/j.neuroscience.2008.06.009 |
| 文献子类 | Article |
| 英文摘要 | Blocking specific K+ channels has been proposed as a promising strategy for the treatment of neurodegenerative diseases. Using a computational virtual screening approach and electrophysiological testing, we found four Aconitum alkaloids are potent blockers of the delayed rectifier K+ channel in rat hippocampal neurons. In the present study, we first tested the action of the four alkaloids on the voltagegated K+, Na+ and Ca2+ currents in rat hippocampal neurons, and then identified that talatisamine is a specific blocker for the delayed rectifier K+ channel. External application of talatisamine reversibly inhibited the delayed rectifier K+ current (I-K)with an IC50 value of 146.0 +/- 5.8 mu M in a voltage-dependent manner, but exhibited very slight blocking effect on the voltagegated Na+ and Ca2+ currents even at the high concentration of 1-3 mM. Moreover, talatisamine exerted a significant hyperpolarizing shift of the steady-state activation, but did not influence the steady state inactivation of I-K and its recovery from inactivation, suggesting that talatisamine had no allosteric action on I-K channel and was a pure blocker binding to the external pore entry of the channel. Our present study made the first discovery of potent and specific I-K channel blocker from Aconitum alkaloids. It has been argued that suppressing K+ efflux by blocking I-K channel may be favorable for Alzheimer's disease therapy. Talatisamine can therefore be considered as a leading compound worthy of further investigations. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved. |
| WOS关键词 | OUTWARD POTASSIUM CURRENT ; ELECTROPHYSIOLOGICAL ASSAY ; ALZHEIMERS-DISEASE ; PYRAMIDAL NEURONS ; ION CHANNELS ; CELL-DEATH ; APOPTOSIS ; BINDING ; ENHANCEMENT ; ALKALOIDS |
| 资助项目 | National Natural Science Foundation of China[30472086] ; Shanghai Education Committee[ZDXK2001] ; Specialized Research Fund for Outstanding Young Teachers of Shanghai Education Committee (2005)[00000000] |
| WOS研究方向 | Neurosciences & Neurology |
| 语种 | 英语 |
| WOS记录号 | WOS:000258909300017 |
| 出版者 | PERGAMON-ELSEVIER SCIENCE LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/272838]  |
| 专题 | 药理学第二研究室 中科院受体结构与功能重点实验室 新药研究国家重点实验室 药理学第一研究室 |
| 通讯作者 | Hu, G. -Y. |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 2.Shanghai Jiao Tong Univ, Sch Med, Inst Med Sci, Shanghai 200025, Peoples R China |
| 推荐引用方式 GB/T 7714 | Song, M. -K.,Liu, H.,Jiang, H. -L.,et al. Discovery of talatisamine as a novel specific blocker for the delayed rectifier K+ channels in rat hippocampal neurons[J]. NEUROSCIENCE,2008,155(2):469-475. |
| APA | Song, M. -K.,Liu, H.,Jiang, H. -L.,Yue, J. M.,Hu, G. -Y.,&Chen, H. -Z..(2008).Discovery of talatisamine as a novel specific blocker for the delayed rectifier K+ channels in rat hippocampal neurons.NEUROSCIENCE,155(2),469-475. |
| MLA | Song, M. -K.,et al."Discovery of talatisamine as a novel specific blocker for the delayed rectifier K+ channels in rat hippocampal neurons".NEUROSCIENCE 155.2(2008):469-475. |
入库方式： OAI收割
来源：上海药物研究所
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