Donepezil blocks voltage-gated ion channels in rat dissociated hippocampal neurons

doi:10.1016/j.ejphar.2004.12.004

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	Donepezil blocks voltage-gated ion channels in rat dissociated hippocampal neurons
	Yu, B; Hu, GY
刊名	EUROPEAN JOURNAL OF PHARMACOLOGY
	2005-01-31
卷号	508 期号:1-3 页码:15-21
关键词	Alzheimer's disease cholinesterase inhibitor Donepezil (E2020) Na+ channel K+ channel
ISSN号	0014-2999
DOI	10.1016/j.ejphar.2004.12.004
文献子类	Article
英文摘要	Donepezil (E2020) is a novel cholinesterase inhibitor for the treatment of Alzheimer's disease. Recent studies show that it may act on targets other than acetylcliolinesterase in the brain. In the present study, the actions of donepezil on voltage-gated Na+ and K+ channels were investigated in rat dissociated hippocampal neurons. Donepezil reversibly inhibited voltage-activated Na+ current (I-Na), delayed rectifier K+ current (I-K) and fast transient K+ current (I-A). The inhibition of donepezil on I-Na was dependent on the holding potential. When neurons were held at -100, -80 and -60 mV, the IC50 value was 436 +/- 19, 291 +/- 26 and 3.8 +/- 0.3 muM, respectively. The drug did not affect the activation, fast inactivation of I-Na and its recovery from fast inactivation. The inhibition of donepezil on I-K (IC50=78 +/- 5 muM) was voltage-dependent, whereas that on I-A (IC50 = 249 +/- 25 muM) was voltage-in dependent. Donepezil caused a significant hyperpolarizing shift of the voltage-dependence of the activation and steady-state inactivation of I-K, without affecting the kinetic properties of I-A. Due to the high concentrations used, the blocking effects of donepezil on the voltage-gated ion channels are unlikely to contribute to the clinical benefits in patients with Alzheimer's disease. (C) 2004 Elsevier B.V. All rights reserved.
WOS关键词	OXYGEN-GLUCOSE DEPRIVATION ; POTASSIUM CURRENT ; PYRAMIDAL NEURONS ; HUPERZINE-A ; GLUTAMATE NEUROTOXICITY ; DELAYED RECTIFIER ; CORTICAL-NEURONS ; INHIBITORS ; DISEASE ; CA1
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	ELSEVIER SCIENCE BV
WOS记录号	WOS:000226894000003
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/273936]
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, GY
作者单位	Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Yu, B,Hu, GY. Donepezil blocks voltage-gated ion channels in rat dissociated hippocampal neurons[J]. EUROPEAN JOURNAL OF PHARMACOLOGY,2005,508(1-3):15-21.
APA	Yu, B,&Hu, GY.(2005).Donepezil blocks voltage-gated ion channels in rat dissociated hippocampal neurons.EUROPEAN JOURNAL OF PHARMACOLOGY,508(1-3),15-21.
MLA	Yu, B,et al."Donepezil blocks voltage-gated ion channels in rat dissociated hippocampal neurons".EUROPEAN JOURNAL OF PHARMACOLOGY 508.1-3(2005):15-21.