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

Ewan St J Smith, Xuming Zhang, Hervé Cadiou, Peter A McNaughton

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

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 ASIC1a and ASIC2a, demonstrating that ion transport is intact in this mutant. These five sites may be involved in the activation of ASIC2a by protons.

Original languageEnglish
Pages (from-to)12-17
Number of pages6
JournalNeuroscience Letters
Volume426
Issue number1
Early online date8 Aug 2007
DOIs
Publication statusPublished - 9 Oct 2007

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Acid Sensing Ion Channels
Protons
Binding Sites
Ion Transport
Site-Directed Mutagenesis
Immunohistochemistry
Cell Membrane
Acids

Keywords

  • Acid Sensing Ion Channels
  • Amino Acid Sequence
  • Amino Acid Substitution
  • Animals
  • Binding Sites
  • CHO Cells
  • Cell Membrane
  • Cricetinae
  • Cricetulus
  • Degenerin Sodium Channels
  • Epithelial Sodium Channels
  • Hydrogen-Ion Concentration
  • Ion Channel Gating
  • Membrane Potentials
  • Membrane Proteins
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Mutation
  • Nerve Tissue Proteins
  • Patch-Clamp Techniques
  • Protons
  • Sodium Channels

Cite this

Proton binding sites involved in the activation of acid-sensing ion channel ASIC2a. / Smith, Ewan St J; Zhang, Xuming; Cadiou, Hervé; McNaughton, Peter A.

In: Neuroscience Letters, Vol. 426, No. 1, 09.10.2007, p. 12-17.

Research output: Contribution to journalArticle

Smith, Ewan St J ; Zhang, Xuming ; Cadiou, Hervé ; McNaughton, Peter A. / Proton binding sites involved in the activation of acid-sensing ion channel ASIC2a. In: Neuroscience Letters. 2007 ; Vol. 426, No. 1. pp. 12-17.
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abstract = "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 ASIC1a and ASIC2a, demonstrating that ion transport is intact in this mutant. These five sites may be involved in the activation of ASIC2a by protons.",
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