Impaired Thermosensation in Mice Lacking TRPV3, a Heat and Camphor Sensor in the Skin

American Association for the Advancement of Science (AAAS) - Tập 307 Số 5714 - Trang 1468-1472 - 2005
Aziz Moqrich1,2, Sun Wook Hwang1,2, Taryn J. Earley1,2, Matt Petrus1,2, Amber N. Murray1,2, Kathryn S.R. Spencer1,2, Mary Andahazy1,2, Gina M. Story1,2, Ardem Patapoutian1,2
1Department of Cell Biology, Scripps Research Institute, La Jolla, CA 92037 USA
2Genomics Institute, Novartis Research Foundation, San Diego, CA 92121, USA.

Tóm tắt

Environmental temperature is thought to be directly sensed by neurons through their projections in the skin. A subset of the mammalian transient receptor potential (TRP) family of ion channels has been implicated in this process. These “thermoTRPs” are activated at distinct temperature thresholds and are typically expressed in sensory neurons. TRPV3 is activated by heat (>33°C) and, unlike most thermoTRPs, is expressed in mouse keratinocytes. We found that TRPV3 null mice have strong deficits in responses to innocuous and noxious heat but not in other sensory modalities; hence, TRPV3 has a specific role in thermosensation. The natural compound camphor, which modulates sensations of warmth in humans, proved to be a specific activator of TRPV3. Camphor activated cultured primary keratinocytes but not sensory neurons, and this activity was abolished in TRPV3 null mice. Therefore, heat-activated receptors in keratinocytes are important for mammalian thermosensation.

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We thank M. Bandell B. Conti H. Esendencia P. Garrity S. Kupriyanov M. Mayford A. Peier L. Reijmers M. Wood and J. Watson for input and assistance; M. Caterina for sharing a detailed protocol on primary culture of keratinocytes; T. Bartfai for sharing the thermal gradient platform; and N. Hong T. Jegla U. Mueller and L. Stowers for critical reading of the manuscript. Supported by National Institute of Neurological Disorders and Stroke grants R01NS046303 and R01NS42822. G.M.S. is a recipient of a National Research Service Award postdoctoral fellowship from NIH. A.P. is a Damon Runyon Scholar.

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American Association for the Advancement of Science (AAAS)

Tập 307 Số 5714

1468-1472

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