title: An ion channel essential for sensing chemical damage.
abstract: Tissue damage and its downstream consequences are experimentally assayed by formaldehyde application, which indiscriminately modifies proteins and is presumed to cause pain through broadly acting mechanisms. Here we show that formaldehyde activates the ion channel TRPA1 and that TRPA1-deficient mice exhibit dramatically reduced formaldehyde-induced pain responses. 4-Hydroxynonenal, a reactive chemical produced endogenously during oxidative stress, and other related aldehydes also activate TRPA1 in vitro. Furthermore, painful responses to iodoacetamide, a nonspecific cysteine-alkylating compound, are abolished in TRPA1-deficient mice. Therefore, although these reactive chemicals modify many proteins, the associated pain appears mainly dependent on a single ion channel.
authors.affiliation: Department of Cell Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
authors.forename: Lindsey J
authors.initials: LJ
authors.lastname: Macpherson
authors.forename: Bailong
authors.initials: B
authors.lastname: Xiao
authors.forename: Kelvin Y
authors.initials: KY
authors.lastname: Kwan
authors.forename: Matt J
authors.initials: MJ
authors.lastname: Petrus
authors.forename: Adrienne E
authors.initials: AE
authors.lastname: Dubin
authors.forename: SunWook
authors.initials: S
authors.lastname: Hwang
authors.forename: Benjamin
authors.initials: B
authors.lastname: Cravatt
authors.forename: David P
authors.initials: DP
authors.lastname: Corey
authors.forename: Ardem
authors.initials: A
authors.lastname: Patapoutian
mesh_terms: D000447:Aldehydes / Q000633:toxicity; D000818:Animals; D002460:Cell Line; D005557:Formaldehyde / Q000633:toxicity; D006801:Humans; D007460:Iodoacetamide / Q000633:toxicity; D051379:Mice; D018345:Mice, Knockout; D010146:Pain / Q000139:chemically induced* / Q000378:metabolism*; D010147:Pain Measurement / Q000379:methods; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: D000447:Aldehydes; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse; D005557:Formaldehyde; C027576:4-hydroxy-2-nonenal; D007460:Iodoacetamide