Identification of a cold receptor reveals a general role for TRP channels in thermosensation.
The cellular and molecular mechanisms that enable us to sense cold are not well understood. Insights into this process have come from the use of pharmacological agents, such as menthol, that elicit a cooling sensation. Here we have characterized and cloned a menthol receptor from trigeminal sensory neurons that is also activated by thermal stimuli in the cool to cold range. This cold- and menthol-sensitive receptor, CMR1, is a member of the TRP family of excitatory ion channels, and we propose that it functions as a transducer of cold stimuli in the somatosensory system. These findings, together with our previous identification of the heat-sensitive channels VR1 and VRL-1, demonstrate that TRP channels detect temperatures over a wide range and are the principal sensors of thermal stimuli in the mammalian peripheral nervous system.
McKemy
David D
DD
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, California 94143-0450, USA.
Neuhausser
Werner M
WM
Julius
David
D
D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D003001:Cloning, Molecular; D003080:Cold Temperature; D018076:DNA, Complementary; D004594:Electrophysiology; D015870:Gene Expression; D007473:Ion Channels / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D008610:Menthol / Q000378:metabolism*; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000737:chemistry; D009475:Neurons, Afferent / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017386:Sequence Homology, Amino Acid; D050053:TRPM Cation Channels; D013823:Thermoreceptors / Q000502:physiology*; D012668:Trigeminal Ganglion / Q000166:cytology; D014982:Xenopus laevis
D015220:Calcium Channels; D018076:DNA, Complementary; D007473:Ion Channels; D009363:Neoplasm Proteins; D050053:TRPM Cation Channels; C498947:Trpm8 protein, rat; D008610:Menthol; D002118:Calcium