A sensory neuron-specific, proton-gated ion channel

Abstract

Proton-gated channels expressed by sensory neurons are of particular interest because low pH causes pain. Two proton-gated channels, acid-sensing ionic channel (ASIC) and dorsal root ASIC (DRASIC), that are members of the amiloride-sensitive ENaC/Degenerin family are known to be expressed by sensory neurons. Here, we describe the cloning and characterization of an ASIC splice variant, ASIC-β, which contains a unique N-terminal 172 aa, as well as unique 5′ and 3′ untranslated sequences. ASIC-β, unlike ASIC and DRASIC, is found only in a subset of small and large diameter sensory neurons and is absent from sympathetic neurons or the central nervous system. The patterns of expression of ASIC and ASIC-β transcripts in rat dorsal root ganglion neurons are distinct. When expressed in COS-7 cells, ASIC-β forms a functional channel with electrophysiological properties distinct from ASIC and DRASIC. The pH dependency and sensitivity to amiloride of ASIC-β is similar to that described for ASIC, but unlike ASIC, the channel is not permeable to calcium, nor are ASIC-β-mediated currents inhibited by extracellular calcium. The unique distribution of ASIC-β suggests that it may play a specialized role in sensory neuron function.