A sensory neuron-specific, proton-gated ion channel.
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-beta, which contains a unique N-terminal 172 aa, as well as unique 5' and 3' untranslated sequences. ASIC-beta, 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-beta transcripts in rat dorsal root ganglion neurons are distinct. When expressed in COS-7 cells, ASIC-beta forms a functional channel with electrophysiological properties distinct from ASIC and DRASIC. The pH dependency and sensitivity to amiloride of ASIC-beta is similar to that described for ASIC, but unlike ASIC, the channel is not permeable to calcium, nor are ASIC-beta-mediated currents inhibited by extracellular calcium. The unique distribution of ASIC-beta suggests that it may play a specialized role in sensory neuron function.
Molecular Nociception Group, Department of Biology, Medawar Building, University College, Gower Street, London WC1E 6BN, United Kingdom.
C C
CC
Chen
S
S
England
A N
AN
Akopian
J N
JN
Wood
D062565:Acid Sensing Ion Channels; D017398:Alternative Splicing; D000584:Amiloride / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002211:Capsaicin / Q000494:pharmacology; D003001:Cloning, Molecular; D017931:DNA Primers / Q000235:genetics; D062626:Degenerin Sodium Channels; D053503:Epithelial Sodium Channels; D005727:Ganglia, Spinal / Q000378:metabolism; D015870:Gene Expression; D014644:Genetic Variation; D017403:In Situ Hybridization; D015640:Ion Channel Gating; D007473:Ion Channels / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D009475:Neurons, Afferent / Q000378:metabolism*; D011522:Protons; D051381:Rats; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D014162:Transfection
D062565:Acid Sensing Ion Channels; C568425:Asic2 protein, rat; D017931:DNA Primers; D062626:Degenerin Sodium Channels; D053503:Epithelial Sodium Channels; D007473:Ion Channels; D009419:Nerve Tissue Proteins; D011522:Protons; D000584:Amiloride; D002211:Capsaicin