TRPA1 acts as a cold sensor in vitro and in vivo.
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 Ca(2+)-independent and Ca(2+) 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.
Karashima
Yuji
Y
Laboratory of Ion Channel Research, Division of Physiology, Department of Molecular Cell Biology, Campus Gasthuisberg O&N1, Katholieke Universiteit Leuven, Herestraat 49 bus 802, B-3000 Leuven, Belgium.
Talavera
Karel
K
Everaerts
Wouter
W
Janssens
Annelies
A
Kwan
Kelvin Y
KY
Vennekens
Rudi
R
Nilius
Bernd
B
Voets
Thomas
T
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism; D003080:Cold Temperature; D006224:Cricetinae; D003412:Cricetulus; D015640:Ion Channel Gating / Q000187:drug effects; D007700:Kinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D009149:Mustard Plant; D010146:Pain / Q000378:metabolism; D010938:Plant Oils / Q000494:pharmacology; D000074025:TRPA1 Cation Channel; D050053:TRPM Cation Channels / Q000378:metabolism; D013697:Thermosensing; D050051:Transient Receptor Potential Channels / Q000172:deficiency / Q000378:metabolism*; D012668:Trigeminal Ganglion / Q000187:drug effects / Q000378:metabolism
D010938:Plant Oils; D000074025:TRPA1 Cation Channel; D050053:TRPM Cation Channels; C492297:TRPM8 protein, mouse; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse; D002118:Calcium; C027793:mustard oil