Proton binding sites involved in the activation of acid-sensing ion channel ASIC2a

被引:41
作者
Smith, Ewan St. J. [1 ]
Zhang, Xuming [1 ]
Cadiou, Herve [1 ]
McNaughton, Peter A. [1 ]
机构
[1] Univ Cambridge, Dept Pharmacol, Cambridge CB2 1PD, England
基金
英国医学研究理事会; 英国生物技术与生命科学研究理事会;
关键词
ASIC; acid; ion channel; pain; channel gating;
D O I
10.1016/j.neulet.2007.07.047
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Most acid-sensing ion channel,(ASIC) subunits are activated by protons, but ASIC2b (a splice variant of ASIC2a) is acid-insensitive. Differences in protonatable residues between the extracellular loop regions of ASIC2a and ASIC2b may explain this difference. Site-directed mutagenesis, combined with immunocytochemistry and whole-cell patch clamp, demonstrated that mutating any one of five ASIC2a sites produces channels that traffic normally to the cell surface membrane but are insensitive to protons. One of the mutants forms functional heteromers with ASIC I a and ASIC2a, demonstrating that ion transport is intact in this mutant. These five sites may be involved in the activation of ASIC2a by protons. (C) 2007 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:12 / 17
页数:6
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