Premium
Molecular Cloning and Regional Distribution of a Human Proton Receptor Subunit with Biphasic Functional Properties
Author(s) -
Babinski Kazimierz,
Lê KhanhTuoc,
Séguéla Philippe
Publication year - 1999
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1999.0720051.x
Subject(s) - acid sensing ion channel , xenopus , homomeric , ion channel , sodium channel , biology , protein subunit , microbiology and biotechnology , amiloride , chemistry , biochemistry , receptor , gene , sodium , organic chemistry
: Small changes of extracellular pH activate depolarizinginward currents in most nociceptive neurons. It has been recently proposedthat acid sensitivity of sensory as well as central neurons is mediated by afamily of proton‐gated cation channels structurally related to Caenorhabditis elegans degenerins and mammalian epithelial sodiumchannels. We describe here the molecular cloning of a novel human protonreceptor, hASIC3, a 531‐amino acid‐long subunit homologous to rat DRASIC.Expression of homomeric hASIC3 channels in Xenopus oocytes generatedbiphasic inward currents elicited at pH <5, providing the first functionalevidence of a human proton‐gated ion channel. Contrary to the DRASIC currentphenotype, the fast desensitizing early component and the slow sustained latecomponent differed both by their cationic selectivity and by their response tothe antagonist amiloride, but not by their pH sensitivity (pH 50 = 3.66 vs. 3.82). Using RT‐PCR and mRNA blot hybridization, we detected hASIC3 mRNA in sensory ganglia, brain, and many internal tissues including lung and testis, so hASIC3 gene expression was not restricted to peripheral sensory neurons. These functional and anatomical data strongly suggest that hASIC3 plays a major role in persistent proton‐induced currents occurring in physiological and pathological conditions of pH changes, likely through a tissue‐specific heteropolymerization with other members of the proton‐gated channel family.