Proton binding sites involved in the activation of acid-sensing ion channel ASIC2a.
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.
Smith
Ewan St J
ES
Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, United Kingdom.
Zhang
Xuming
X
Cadiou
Hervé
H
McNaughton
Peter A
PA
D062565:Acid Sensing Ion Channels; D000595:Amino Acid Sequence / Q000235:genetics; D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D001665:Binding Sites / Q000502:physiology; D016466:CHO Cells; D002462:Cell Membrane / Q000737:chemistry* / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D062626:Degenerin Sodium Channels; D053503:Epithelial Sodium Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D015640:Ion Channel Gating / Q000235:genetics; D008564:Membrane Potentials / Q000235:genetics; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011522:Protons; D015222:Sodium Channels / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
D062565:Acid Sensing Ion Channels; D062626:Degenerin Sodium Channels; D053503:Epithelial Sodium Channels; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011522:Protons; D015222:Sodium Channels