Mechanism of TRPA1 Activation

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DESCRIPTION (provided by applicant): The overall objective of this proposal is to contribute to the understanding of the mechanisms that underlie thermosensation. The sensation of temperature and the ability to regulate body temperature based on those sensations is a very basic requirement of mammalian biology. Despite the basic nature of this process, little is known about exactly how the body can sense temperature. Recently, members of the TRP family of non-selective cation channels have been shown to be activated in response to different temperature ranges. Many of these "thermoTRPs" are also able to respond to natural compounds which produce a burning, cooling, or prickling pungency through the sensation known as chemesthesis. TRPA1, a noxious cold sensing channel expressed in the pain-sensing neurons innervating the mouth and tongue, is also able to be activated by pungent compounds. Cinnamaldehyde, allyl isothiocyanate, and allicin activate TRPA1 and produce the characteristic burning, prickling sensations of cinnamon red-hots, wasabi, and raw garlic. In this proposal, I will investigate the molecular mechanisms involved in TRPA1's activation by cold and pungent chemical stimuli.