Calcium-permeable acid-sensing ion channel is a molecular target of the neurotoxic metal ion lead

CORC > 昆明动物研究所 > 昆明动物研究所 > 动物模型与人类重大疾病机理重点实验室 > 学习记忆的分子神经机制

	Calcium-permeable acid-sensing ion channel is a molecular target of the neurotoxic metal ion lead
	Wang W 1,2; Duan B 1,2; Xu H 1,2; Xu L[]3; Xu TL[]1,2
刊名	JOURNAL OF BIOLOGICAL CHEMISTRY
	2006
卷号	281 期号:5 页码:2497-2505
通讯作者	lxu@vip.163.com ; tlxu@ion.ac.cn
合作状况	其它
英文摘要	Acid-sensing ion channels (ASICs) are emerging as fundamental players in the regulation of neural plasticity and in pathological conditions. Here we showed that lead (Pb2+), a well known neurotoxic metal ion, reversibly and concentration-dependently inhibited ASIC currents in the acutely dissociated spinal dorsal horn and hippocampal CA1 neurons of rats. In vitro expression of ASIC subunits in combination demonstrated that both ASIC1 and -3 subunits were sensitive to Pb2+. Mechanistically, Pb2+ reduced the pH sensitivity of ASICs independent of membrane voltage change. Moreover, Pb2+ inhibited the ASIC-mediated membrane depolarization and the elevation of intracellular Ca2+ concentration. In addition, we compared the effect of Pb2+ with that of Ca2+ or amiloride to explore the possible interactions of Pb2+ and Ca2+ in regulating ASICs, and we found that Pb2+ inhibited ASIC currents independent of the amiloride/Ca2+ blockade. Because ASIC1b and -3 subunits are mainly expressed in peripheral neurons, our data identified ASIC1a-containing Ca2+-permeable ASIC as a novel central target of Pb2+ action, which may contribute to Pb2+ neurotoxicity.
收录类别	SCI
资助信息	This work was supported by the National Natural Science Foundation of China Grants 30125015 and 30321002, the National Basic Research Program of China Grant 2006CB500803,andtheShanghaiMunicipalGovernment.Thecostsofpublicationof this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
语种	英语
内容类型	期刊论文
源URL	[http://159.226.149.26:8080/handle/152453/10583]
专题	昆明动物研究所_学习记忆的分子神经机制
作者单位	1.Chinese Acad Sci, Shanghai Inst Biol Sci, Key Lab Neurobiol, Shanghai 200031, Peoples R China 2.Univ Sci & Technol China, Sch Life Sci, Hefei 230027, Peoples R China 3.Chinese Acad Sci, Lab Learning & Memory, Kunming Inst Zool, Kunming 650223, Yunnan, Peoples R China
推荐引用方式 GB/T 7714	Wang W,Duan B,Xu H,et al. Calcium-permeable acid-sensing ion channel is a molecular target of the neurotoxic metal ion lead[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2006,281(5):2497-2505.
APA	Wang W,Duan B,Xu H,Xu L[],&Xu TL[].(2006).Calcium-permeable acid-sensing ion channel is a molecular target of the neurotoxic metal ion lead.JOURNAL OF BIOLOGICAL CHEMISTRY,281(5),2497-2505.
MLA	Wang W,et al."Calcium-permeable acid-sensing ion channel is a molecular target of the neurotoxic metal ion lead".JOURNAL OF BIOLOGICAL CHEMISTRY 281.5(2006):2497-2505.