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Title: Calcium-permeable acid-sensing ion channel is a molecular target of the neurotoxic metal ion lead
Author: Wang, W ; Duan, B ; Xu, H ; Xu, L ; Xu, TL(徐天乐)
Source: JOURNAL OF BIOLOGICAL CHEMISTRY
Issued Date: 2006
Volume: 281, Issue:5, Pages:2497-2505
Keyword: LONG-TERM POTENTIATION ; PROTEIN-KINASE-C ; RAT HIPPOCAMPAL-NEURONS ; SYNAPTIC PLASTICITY ; SENSORY NEURONS ; NA+ CHANNEL ; CA2+ ; CONTRIBUTES ; INCREASES ; EXPOSURE
Subject: Biochemistry & Molecular Biology
Corresponding Author: Xu, L (reprint author), Chinese Acad Sci, Lab Learning & Memory, Kunming Inst Zool, 32 Jiaochang Donglu, Kunming 650223, Yunnan, Peoples R China,lxu@vip.163.com
English Abstract: 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.
Indexed Type: SCI
Language: 英语
Content Type: 期刊论文
URI: http://ir.sibs.ac.cn/handle/331001/1838
Appears in Collections:神经所(总)_期刊论文

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Wang, W; Duan, B; Xu, H; Xu, L; Xu, TL.Calcium-permeable acid-sensing ion channel is a molecular target of the neurotoxic metal ion lead,JOURNAL OF BIOLOGICAL CHEMISTRY,2006,281(5):2497-2505
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