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

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

doi:10.1016/j.neulet.2007.07.047

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

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

College of Health and Life Sciences

Research output: Contribution to journal › Article › peer-review

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 language	English
Pages (from-to)	12-17
Number of pages	6
Journal	Neuroscience Letters
Volume	426
Issue number	1
DOIs	https://doi.org/10.1016/j.neulet.2007.07.047
Publication status	Published - 9 Oct 2007

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
Journal Article
Research Support, Non-U.S. Gov't

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10.1016/j.neulet.2007.07.047

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title = "Proton binding sites involved in the activation of acid-sensing ion channel ASIC2a",

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.",

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, Journal Article, Research Support, Non-U.S. Gov't",

author = "Smith, {Ewan St J} and Xuming Zhang and Herv{\'e} Cadiou and McNaughton, {Peter A}",

year = "2007",

month = oct,

day = "9",

doi = "10.1016/j.neulet.2007.07.047",

language = "English",

volume = "426",

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journal = "Neuroscience Letters",

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T1 - Proton binding sites involved in the activation of acid-sensing ion channel ASIC2a

AU - Smith, Ewan St J

AU - Zhang, Xuming

AU - Cadiou, Hervé

AU - McNaughton, Peter A

PY - 2007/10/9

Y1 - 2007/10/9

N2 - 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.

AB - 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.

KW - Acid Sensing Ion Channels

KW - Amino Acid Sequence

KW - Amino Acid Substitution

KW - Animals

KW - Binding Sites

KW - CHO Cells

KW - Cell Membrane

KW - Cricetinae

KW - Cricetulus

KW - Degenerin Sodium Channels

KW - Epithelial Sodium Channels

KW - Hydrogen-Ion Concentration

KW - Ion Channel Gating

KW - Membrane Potentials

KW - Membrane Proteins

KW - Molecular Sequence Data

KW - Mutagenesis, Site-Directed

KW - Mutation

KW - Nerve Tissue Proteins

KW - Patch-Clamp Techniques

KW - Protons

KW - Sodium Channels

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.neulet.2007.07.047

DO - 10.1016/j.neulet.2007.07.047

M3 - Article

C2 - 17881127

SN - 0304-3940

VL - 426

SP - 12

EP - 17

JO - Neuroscience Letters

JF - Neuroscience Letters

IS - 1

ER -

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

Abstract

Keywords

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