Identification of a cold receptor reveals a general role for TRP channels in thermosensation

Nature. 2002 Mar 7;416(6876):52-8. doi: 10.1038/nature719. Epub 2002 Feb 10.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Calcium / metabolism
  • Calcium Channels / chemistry
  • Calcium Channels / genetics
  • Calcium Channels / physiology
  • Cells, Cultured
  • Cloning, Molecular
  • Cold Temperature*
  • DNA, Complementary
  • Electrophysiology
  • Gene Expression
  • Ion Channels / chemistry
  • Ion Channels / genetics
  • Ion Channels / physiology*
  • Menthol / metabolism*
  • Molecular Sequence Data
  • Neoplasm Proteins / chemistry
  • Neurons, Afferent / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Sequence Homology, Amino Acid
  • TRPM Cation Channels
  • Thermoreceptors* / physiology*
  • Trigeminal Ganglion / cytology
  • Xenopus laevis


  • Calcium Channels
  • DNA, Complementary
  • Ion Channels
  • Neoplasm Proteins
  • TRPM Cation Channels
  • Trpm8 protein, rat
  • Menthol
  • Calcium

Associated data

  • GENBANK/AY072788