title: TRPA1 is a component of the nociceptive response to CO2.
abstract: In humans, high concentrations of CO(2), as found in carbonated beverages, evoke a mixture of sensations that include a stinging or pungent quality. The stinging sensation is thought to originate with the activation of nociceptors, which innervate the respiratory, nasal, and oral epithelia. The molecular basis for this sensation is unknown. Here we show that CO(2) specifically activates a subpopulation of trigeminal neurons that express TRPA1, a mustard oil- and cinnamaldehyde-sensitive channel, and that these responses are dependent on a functional TRPA1 gene. TRPA1 is sufficient to mediate responses to CO(2) as TRPA1 channels expressed in HEK-293 cells, but not TRPV1 channels, were activated by bath-applied CO(2). CO(2) can diffuse into cells and produce intracellular acidification, which could gate TRPA1 channels. Consistent with this mechanism, TRPA1 channels in excised patches were activated in a dose-dependent manner by intracellular protons. We conclude that TRPA1, by sensing intracellular acidification, constitutes an important component of the nociceptive response to CO(2).
authors.affiliation: Department of Biological Sciences, Section of Neurobiology, University of Southern California, Los Angeles, California 90089, USA.
authors.forename: Yuanyuan Y
authors.initials: YY
authors.lastname: Wang
authors.forename: Rui B
authors.initials: RB
authors.lastname: Chang
authors.forename: Emily R
authors.initials: ER
authors.lastname: Liman
mesh_terms: D000171:Acrolein / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002245:Carbon Dioxide / Q000502:physiology*; D002460:Cell Line; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009055:Mouth / Q000187:drug effects / Q000294:innervation; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques / Q000379:methods; D051381:Rats; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000502:physiology*; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels / Q000819:agonists / Q000096:biosynthesis / Q000502:physiology*; D014276:Trigeminal Nerve / Q000187:drug effects / Q000502:physiology*
chemical_list: D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse; D002245:Carbon Dioxide; D000171:Acrolein; C012843:cinnamaldehyde