A SENSORY NEURON-SPECIFIC, PROTON-GATED ION-CHANNEL

Proton-gated channels expressed by sensory neurons are of particular i nterest because low pH causes pain. Two proton-gated channels, acid-se nsing ionic channel (ASIC) and dorsal root ASIC (DRASIC), that are mem bers of the amiloride-sensitive ENaC/Degenerin family are known to be expressed by sensory neurons. Here, we describe the cloning and charac terization of an ASIC splice variant, ASIC-beta, which contains a uniq ue N-terminal 172 aa, as well as unique 5' and 3' untranslated sequenc es. ASIC-beta, unlike ASIC and DRASIC, is found only in a subset of sm all and large diameter sensory neurons and is absent from sympathetic neurons or the central nervous system. The patterns of expression of A SIC and ASIC-P transcripts in rat dorsal root ganglion neurons are dis tinct When expressed in COS-7 cells, ASIC-beta farms a functional chan nel with electrophysiological properties distinct from ASIC and DRASIC . The pH dependency and sensitivity to amiloride of ASIC-beta is simil ar to that described for ASIC, but unlike ASIC, the channel is not per meable to calcium, nor are ASIC-beta-mediated currents inhibited by ex tracellular calcium. The unique distribution of ASIC-beta suggests tha t it may play a specialized role in sensory neuron function.