Acid-sensing ion channels (ASICs) are cationic channels activated by extracellular protons. They are expressed in sensory neurons, where they are thought to be involved in @entity158 perception associated with tissue @entity520 . They are also expressed in brain. A number of brain regions, like the hippocampus, contain large amounts of chelatable vesicular @entity8862 . This paper shows that @entity8862 potentiates the acid activation of homomeric and heteromeric @entity16476 -containing channels (i.e. @entity16476 , ASIC1a+2a, @entity16476 +3), but not of homomeric ASIC1a and @entity59909 . The EC(50) for @entity8862 potentiation is 120 and 111 microm for the @entity16476 and ASIC1a+2a current, respectively. @entity8862 shifts the pH dependence of activation of the ASIC1a+2a current from a pH(0.5) of 5.5 to 6.0. Systematic mutagenesis of the 10 extracellular histidines of @entity16476 leads to the identification of two residues (His-162 and His-339) that are essential for the @entity8862 potentiating effect. Mutation of another @entity3793 residue, His-72, abolishes the pH sensitivity of @entity16476 . This residue, which is located just after the first transmembrane domain, seems to be an essential component of the extracellular pH sensor of @entity16476 .

XXXX and H+ are coactivators of acid-sensing ion channels.

@entity8862 :: ('CHEBI:37256', 'Chemical') :: ['Zn(2+)'] @entity3793 :: ('CHEBI:27570', 'Chemical') :: ['histidine'] @entity16476 :: ('40', 'Gene') :: ['ASIC2a'] @entity59909 :: ('9311', 'Gene') :: ['ASIC3'] @entity520 :: ('MESH:D000138', 'Disease') :: ['acidosis'] @entity158 :: ('MESH:D010146', 'Disease') :: ['pain']
@entity8862 :: (CHEBI:37256,Chemical) :: ['Zn2+']
