TRPM8 channel

Channel name TRPM81,2,3,4,5
Description Cooling and menthol-sensing TRP channel
Other names CMR1 (cold and menthol receptor), Trp-p8
Molecular information Human unigene: Hs0.366053, chr. 2q37.1
Mouse unigene: Mm0.218753, chr. 1 D
Associated subunits Not established
Functional assays Patch-clamp, calcium imaging
Current Steeply outwardly rectifying >0 mV
Conductance 83pS (slope conductance)
Ion selectivity PNa/PCa = 0.3, nonselective cation channel
Activation 8–26°C
Inactivation Warming >28°C
Activators Cooling below 22–26°C, cooling agents such as menthol (EC50 = 70 μM) and icilin (EC50 = 360 nM); less potent: linalool, geraniol, hydroxycitronella
Gating inhibitors None
Blockers BCTC, thio-BCTC, capsazepine
Radioligands None
Channel distribution Small sensory neurons of trigeminal ganglion and dorsal root ganglia, prostate epithelium
Physiological functions Cold sensation
Mutations and pathophysiology Not established
Pharmacological significance Putative menthol receptor
Comments The neuronal colocalization and potential coassembly of TRPV1, TRPV2, TRPV3, and TRPM8 are under study
  • chr., chromosome.

  • 1. McKemy DD, Neuhausser WM, and Julius D (2002) Identification of a cold receptor reveals a general role for TRP channels in thermosensation. Nature (Lond) 416:52-58

  • 2. Peir AM, Moqrich A, Hergarden AC, Reeve AJ, Andersson DA, Story GM, Earley TJ, Dragoni I, McIntyre P, Bevan S, et al. (2002) A TRP channel that senses cold stimuli and menthol. Cell 108:705-715

  • 3. Voets T, Droogmans G, Wissenbach U, Janssens A, Flockerzi V, and Nilius B (2004) The principle of temperature-dependent gating in cold- and heat-sensitive TRP channels. Nature (Lond) 430:748-754

  • 4. Brauchi S, Orio P, and Latorre R (2004) Clues to understanding cold sensation: thermodynamics and electrophysiological analysis of the cold receptor TRPM8. Proc Natl Acad Sci USA 101:15494-15499

  • 5. Behrendt HJ, Germann T, Gillen C, Hatt H, and Jostock R (2004) Characterization of the mouse cold-menthol receptor TRPM8 and vanilloid receptor type-1 VR1 using a fluorometric imaging plate reader (FLIPR) assay. Br J Pharmacol 141:737-745