TRPA1 acts as a cold sensor in vitro and in vivo

Yuji Karashima, Karel Talavera, Wouter Everaerts, Annelies Janssens, Kelvin Y. Kwan, Rudi Vennekens, Bernd Nilius, Thomas Voets

Research output: Contribution to journalArticlepeer-review

463 Citations (Scopus)


TRPA1 functions as an excitatory ionotropic receptor in sensory neurons. It was originally described as a noxious cold-activated channel, but its cold sensitivity has been disputed in later studies, and the contribution of TRPA1 to thermosensing is currently a matter of strong debate. Here, we provide several lines of evidence to establish that TRPA1 acts as a cold sensor in vitro and in vivo. First, we demonstrate that heterologously expressed TRPA1 is activated by cold in a Ca2+-independent and Ca2+ store-independent manner; temperature-dependent gating of TRPA1 is mechanistically analogous to that of other temperature-sensitive TRP channels, and it is preserved after treatment with the TRPA1 agonist mustard oil. Second, we identify and characterize a specific subset of cold-sensitive trigeminal ganglion neurons that is absent in TRPA1-deficient mice. Finally, cold plate and tail-flick experiments reveal TRPA1-dependent, cold-induced nociceptive behavior in mice. We conclude that TRPA1 acts as a major sensor for noxious cold.

Original languageEnglish
Pages (from-to)1273-1278
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number4
Publication statusPublished - Jan 27 2009
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General


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