Identification, functional expression and chromosomal localisation of a sustained human proton-gated cation channel.
Non-inactivating or slowly inactivating proton-gated cation channels are thought to play an important role in the perception of pain that accompanies tissue acidosis. We have identified a novel human proton-gated cation channel subunit that has biphasic desensitisation kinetics with both a rapidly inactivating Na+-selective and a sustained component. The protein shares 84% sequence identity with the proton-gated cation channel rASIC3 (rDRASIC) from rat sensory neurones. The biphasic desensitisation kinetics and the sequence homology suggest that this novel clone (hASIC3) is the human orthologue of rASIC3 (rDRASIC). While rASIC3 (rDRASIC) requires very acidic pH (pH < 4.5) for activation of the sustained current, the non-inactivating hASIC3 current starts to be activated when the pH decreases to below pH 6. hASIC3 is an acid sensor and might play an important role in the detection of lasting pH changes in human. We localised the hASIC3 gene to the human chromosome 7q35, 6.4 cRad telomeric from the microsatellite AFMA082XC9.
de Weille
J R
JR
Institut de Pharmacologie Moléculaire et Cellulaire, CNRS, Valbonne, France.
Bassilana
F
F
Lazdunski
M
M
Waldmann
R
R
D062565:Acid Sensing Ion Channels; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002874:Chromosome Mapping; D002897:Chromosomes, Human, Pair 7; D005819:Genetic Markers; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008565:Membrane Proteins; D018895:Microsatellite Repeats; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins; D009475:Neurons, Afferent / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015222:Sodium Channels / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D016615:Telomere; D014162:Transfection
C112231:ASIC3 protein, human; D062565:Acid Sensing Ion Channels; D005819:Genetic Markers; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011994:Recombinant Proteins; D015222:Sodium Channels