Discovery of talatisamine as a novel specific blocker for the delayed rectifier K+ channels in rat hippocampal neurons

doi:10.1016/j.neuroscience.2008.06.009

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	Discovery of talatisamine as a novel specific blocker for the delayed rectifier K+ channels in rat hippocampal neurons
	Song, M. -K.1,2; Liu, H.1 ; Jiang, H. -L.1; Yue, J. M.1; Hu, G. -Y.1; Chen, H. -Z.2
刊名	NEUROSCIENCE
	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.
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关键词	OUTWARD POTASSIUM CURRENT ; ELECTROPHYSIOLOGICAL ASSAY ; ALZHEIMERS-DISEASE ; PYRAMIDAL NEURONS ; ION CHANNELS ; CELL-DEATH ; APOPTOSIS ; BINDING ; ENHANCEMENT ; ALKALOIDS
WOS研究方向	Neurosciences & Neurology
语种	英语
出版者	PERGAMON-ELSEVIER SCIENCE LTD
WOS记录号	WOS:000258909300017
内容类型	期刊论文
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.