Abstract: 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 ant acid sensor and might play an important role in the detection of lasting pH changes in human. We localized the hASIC3 gene to the human chromosome 7q35, 6.