A sensory neuron-specific, proton-gated ion channel

Chih‐Cheng Chen1, Steven England1, Armen N. Akopian1, John N. Wood1
1Molecular Nociception Group, Department of Biology, Medawar Building, University College, Gower Street, London WC1E 6BN, United Kingdom.

Tóm tắt

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.

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