Impaired thermosensation in mice lacking TRPV3, a heat and camphor sensor in the skin.
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 degrees 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.
Moqrich
Aziz
A
Department of Cell Biology, Scripps Research Institute, La Jolla, CA 92037, USA.
Hwang
Sun Wook
SW
Earley
Taryn J
TJ
Petrus
Matt J
MJ
Murray
Amber N
AN
Spencer
Kathryn S R
KS
Andahazy
Mary
M
Story
Gina M
GM
Patapoutian
Ardem
A
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D016466:CHO Cells; D002164:Camphor / Q000494:pharmacology; D027682:Cation Transport Proteins / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D006224:Cricetinae; D020405:Dermis / Q000033:anatomy & histology / Q000294:innervation / Q000648:ultrastructure; D004817:Epidermis / Q000033:anatomy & histology / Q000294:innervation / Q000648:ultrastructure; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism; D006358:Hot Temperature; D006801:Humans; D007473:Ion Channels / Q000235:genetics / Q000502:physiology*; D015603:Keratinocytes / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009475:Neurons, Afferent / Q000502:physiology; D018408:Patch-Clamp Techniques; D050916:TRPV Cation Channels; D013696:Temperature; D013823:Thermoreceptors / Q000502:physiology*; D013697:Thermosensing; D013997:Time Factors
D027682:Cation Transport Proteins; D007473:Ion Channels; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; C486760:Trpv3 protein, mouse; C486576:Trpv4 protein, mouse; D002164:Camphor; D001920:Bradykinin