Referenced in: none

Automatically associated channels: TRP , TRPA , TRPA1

Title: TRPA1 underlies a sensing mechanism for O2.

Authors: Nobuaki Takahashi, Tomoyuki Kuwaki, Shigeki Kiyonaka, Tomohiro Numata, Daisuke Kozai, Yusuke Mizuno, Shinichiro Yamamoto, Shinji Naito, Ellen Knevels, Peter Carmeliet, Toru Oga, Shuji Kaneko, Seiji Suga, Toshiki Nokami, Jun-ichi Yoshida, Yasuo Mori

Journal, date & volume: Nat. Chem. Biol., 2011 Oct , 7, 701-11

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/21873995

Abstract
Oxygen (O(2)) is a prerequisite for cellular respiration in aerobic organisms but also elicits toxicity. To understand how animals cope with the ambivalent physiological nature of O(2), it is critical to elucidate the molecular mechanisms responsible for O(2) sensing. Here our systematic evaluation of transient receptor potential (TRP) cation channels using reactive disulfides with different redox potentials reveals the capability of TRPA1 to sense O(2). O(2) sensing is based upon disparate processes: whereas prolyl hydroxylases (PHDs) exert O(2)-dependent inhibition on TRPA1 activity in normoxia, direct O(2) action overrides the inhibition via the prominent sensitivity of TRPA1 to cysteine-mediated oxidation in hyperoxia. Unexpectedly, TRPA1 is activated through relief from the same PHD-mediated inhibition in hypoxia. In mice, disruption of the Trpa1 gene abolishes hyperoxia- and hypoxia-induced cationic currents in vagal and sensory neurons and thereby impedes enhancement of in vivo vagal discharges induced by hyperoxia and hypoxia. The results suggest a new O(2)-sensing mechanism mediated by TRPA1.