IDENTIFICATION, FUNCTIONAL EXPRESSION AND CHROMOSOMAL LOCALIZATION OFA SUSTAINED HUMAN PROTON-GATED CATION CHANNEL

Non-inactivating or slowly inactivating proton-gated cation channels a re thought to play an important role in the perception of pain that ac companies tissue acidosis. We have identified a novel human proton-gat ed cation channel subunit that has biphasic desensitisation kinetics w ith both a rapidly inactivating Na+-selective and a sustained componen t. The protein shares 84% sequence identity with the proton-gated cati on channel rASIC3 (rDRASIC) from rat sensory neurones. The biphasic de sensitisation kinetics and the sequence homology suggest that this nov el clone (hASIC3) is the human orthologue of rASIC3 (rDRASIC), While r ASIC3 (rDRASIC) requires very acidic pH (pH < 4.5) for activation of t he sustained current, the non-inactivating hASIC3 current starts to be activated when the pH decreases to below pH 6, hASIC3 is an acid sens or and might play an important role in the detection of lasting pH cha nges in human. We localised the hASIC3 gene to the human chromosome 7q 35, 6.4 cRad telomeric from the microsatellite AFMA082XC9. (C) 1998 Fe deration of European Biochemical Societies.