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Science 307 (5714): 1468-1472

Copyright © 2005 by the American Association for the Advancement of Science

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

Aziz Moqrich,1,2* Sun Wook Hwang,1* Taryn J. Earley,1 Matt J. Petrus,2 Amber N. Murray,1 Kathryn S. R. Spencer,1 Mary Andahazy,2 Gina M. Story,1 Ardem Patapoutian1,2{dagger}

Abstract: 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.

1 Department of Cell Biology, Scripps Research Institute, La Jolla, CA 92037, USA.
2 Genomics Institute, Novartis Research Foundation, San Diego, CA 92121, USA.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: ardem{at}scripps.edu

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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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J. Biol. Chem. 281, 25006-25010
   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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J. Neurosci. 25, 8924-8937
   Abstract »    Full Text »    PDF »
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E. de la Pena, A. Malkia, H. Cabedo, C. Belmonte, and F. Viana (2005)
J. Physiol. 567, 415-426
   Abstract »    Full Text »    PDF »
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B. Nilius, K. Talavera, G. Owsianik, J. Prenen, G. Droogmans, and T. Voets (2005)
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   Abstract »    Full Text »    PDF »
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