HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 281, Issue 5, 2497-2505, February 3, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: 281/5/2497    most recent M507123200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wang, W. Articles by Xu, T.-L. Search for Related Content PubMed PubMed Citation Articles by Wang, W. Articles by Xu, T.-L. Social Bookmarking                      What's this?

Calcium-permeable Acid-sensing Ion Channel Is a Molecular Target of the Neurotoxic Metal Ion Lead^*

Wei Wang¹, Bo Duan¹, Han Xu, Lin Xu^¶2, and Tian-Le Xu³

From the Institute of Neuroscience and Key Laboratory of Neurobiology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, the School of Life Sciences, University of Science and Technology of China, Hefei 230027, and the ^¶Laboratory of Learning and Memory, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China

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.

Received for publication, June 30, 2005 , and in revised form, November 28, 2005.

^* 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, and the Shanghai Municipal Government. The costs of publication of 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.

¹ Both authors contributed equally to this work.

² To whom correspondence may be addressed: Laboratory of Learning and Memory, Kunming Institute of Zoology, Chinese Academy of Sciences, 32 Jiaochang Donglu, Kunming 650223, Yunnan, China. Tel.: 86-871-519-5402; Fax: 86-871-519-1823; E-mail: lxu{at}vip.163.com. ³ To whom correspondence may be addressed: Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-yang Road, Shanghai 200031, China. Tel.: 86-21-54921751; Fax: 86-21-54921735; E-mail: tlxu{at}ion.ac.cn.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				H.-R. Kim, G.-H. Lee, K.-C. Ha, T. Ahn, J.-Y. Moon, B.-J. Lee, S.-G. Cho, S. Kim, Y.-R. Seo, Y.-J. Shin, et al. Bax Inhibitor-1 Is a pH-dependent Regulator of Ca2+ Channel Activity in the Endoplasmic Reticulum J. Biol. Chem., June 6, 2008; 283(23): 15946 - 15955. [Abstract] [Full Text] [PDF]

				B. Duan, L.-J. Wu, Y.-Q. Yu, Y. Ding, L. Jing, L. Xu, J. Chen, and T.-L. Xu Upregulation of Acid-Sensing Ion Channel ASIC1a in Spinal Dorsal Horn Neurons Contributes to Inflammatory Pain Hypersensitivity J. Neurosci., October 10, 2007; 27(41): 11139 - 11148. [Abstract] [Full Text] [PDF]

				J.-H. Cho and C. C. Askwith Potentiation of acid-sensing ion channels by sulfhydryl compounds Am J Physiol Cell Physiol, June 1, 2007; 292(6): C2161 - C2174. [Abstract] [Full Text] [PDF]

				F. Mercado, I. A. Lopez, D. Acuna, R. Vega, and E. Soto Acid-Sensing Ionic Channels in the Rat Vestibular Endorgans and Ganglia J Neurophysiol, September 1, 2006; 96(3): 1615 - 1624. [Abstract] [Full Text] [PDF]