PubMed 24071625

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: TRP , TRPA , TRPA1

Title: Species differences and molecular determinant of TRPA1 cold sensitivity.

Authors: Jun Chen, Dawon Kang, Jing Xu, Marc Lake, James O Hogan, Chaohong Sun, Karl Walter, Betty Yao, Donghee Kim

Journal, date & volume: Nat Commun, 2013 Sep 27 , 4, 2501

PubMed link:

TRPA1 is an ion channel and has been proposed as a thermosensor across species. In invertebrate and ancestral vertebrates such as fly, mosquito, frog, lizard and snakes, TRPA1 serves as a heat receptor, a sensory input utilized for heat avoidance or infrared detection. However, in mammals, whether TRPA1 is a receptor for noxious cold is highly controversial, as channel activation by cold was observed by some groups but disputed by others. Here we attribute the discrepancy to species differences. We show that cold activates rat and mouse TRPA1 but not human or rhesus monkey TRPA1. At the molecular level, a single residue within the S5 transmembrane domain (G878 in rodent but V875 in primate) accounts for the observed difference in cold sensitivity. This residue difference also underlies the species-specific effects of menthol. Together, our findings identify the species-specific cold activation of TRPA1 and reveal a molecular determinant of cold-sensitive gating.