Cellular electrophysiological effects of changrolin in isolated rat cardiac myocytes

doi:10.1016/j.ejphar.2010.08.024

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	Cellular electrophysiological effects of changrolin in isolated rat cardiac myocytes
	Chen, Wei-hai 2; Yang, Ding 2; Wang, Wen-yi ; Zhang, Jie ; Wang, Yi-ping1
刊名	EUROPEAN JOURNAL OF PHARMACOLOGY
	2010-11-25
卷号	647 期号:1-3 页码:139-146
关键词	Changrolin Whole-cell patch-clamp Na+ channels K+ channels Ca2+ channels
ISSN号	0014-2999
DOI	10.1016/j.ejphar.2010.08.024
文献子类	Article
英文摘要	Changrolin (2, 6-bis[pyrrolidin-1-ylmethyl]-4-[quinazolin-4-ylamino] phenol) is an anti-arrhythmic drug derived from beta-dichroine, an active component of the Chinese medicinal herb, Dichroa febrifuga Lour. To elucidate the mechanism underlying the anti-arrhythmic effect of changrolin. we used the whole-cell patch-clamp technique to characterize the electrophysiological actions of changrolin in isolated rat cardiomyocytes. In this study, changrolin inhibited delayed rectified K currents (I-K) in a concentration-dependent manner with inhibiting the current by 11.9%+/- 4.7%, 27.8%+/- 3.4%, 31.5%+/- 3.6% and 40.8%+/- 3.7% at 10, 30, 100 and 300 mu M, respectively (n=7-8). Changrolin was less effective against transient outward K+ currents (I-to), and only showed significantly inhibitory effect at the highest concentration (300 mu M). Changrolin also induced a concentration-dependent inhibition of sodium currents (I-Na) with an IC50. of 10.19 mu M (Hill coefficient=-1.727, n=6-7). In addition, changrolin exerted a holding potential-dependent block on Na+ channels, produced a hyperpolarizing shift in the steady-state inactivation curve, as well as exhibited a marked frequency-dependent component to the blockade of Na+ channels. Finally, calcium currents (I-ca) was decreased by changrolin in a concentration-dependent manner with an estimated IC50 of 74.73 mu M (Hill coefficient=-0.9082, n=6). In conclusion, changrolin blocks Na+ and Ca2+ channels, and also blocks K+ channels (I-to and I-K) to some extent. Notably, changrolin preferentially blocks the inactivated state of Na+ channels. These effects lead to a modification of electromechanical function and likely contribute to the termination of arrhythmia. (c) 2010 Elsevier B.V. All rights reserved
资助项目	National Basic Research Program of China[2009CB930300] ; State Key Laboratory of Drug research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences[00000000]
WOS关键词	GUINEA-PIG ; CALCIUM CURRENT ; HEART-CELLS ; DERIVATIVES ; POTASSIUM ; CHANNELS ; DRUGS
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	ELSEVIER SCIENCE BV
WOS记录号	WOS:000283835400019
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/278713]
专题	药理学第一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
通讯作者	Wang, Yi-ping
作者单位	1.Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai Inst Biol Sci,Cardiovasc Pharmacol Lab, Shanghai 201203, Peoples R China; 2.Chinese Acad Sci, Grad Sch, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Chen, Wei-hai,Yang, Ding,Wang, Wen-yi,et al. Cellular electrophysiological effects of changrolin in isolated rat cardiac myocytes[J]. EUROPEAN JOURNAL OF PHARMACOLOGY,2010,647(1-3):139-146.
APA	Chen, Wei-hai,Yang, Ding,Wang, Wen-yi,Zhang, Jie,&Wang, Yi-ping.(2010).Cellular electrophysiological effects of changrolin in isolated rat cardiac myocytes.EUROPEAN JOURNAL OF PHARMACOLOGY,647(1-3),139-146.
MLA	Chen, Wei-hai,et al."Cellular electrophysiological effects of changrolin in isolated rat cardiac myocytes".EUROPEAN JOURNAL OF PHARMACOLOGY 647.1-3(2010):139-146.