Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Sensing with TRP channels

Nature Chemical Biology volume 1, pages 85–92 (2005)Cite this article

Abstract

Drosophila melanogaster flies carrying the trp (transient receptor potential) mutation are rapidly blinded by bright light, because of the absence of a Ca2+-permeable ion channel in their photoreceptors. The identification of the trp gene and the search for homologs in yeast, flies, worms, zebrafish and mammals has led to the discovery of a large superfamily of related cation channels, named TRP channels. Activation of TRP channels is highly sensitive to a variety of chemical and physical stimuli, allowing them to function as dedicated biological sensors that are essential in processes such as vision, taste, tactile sensation and hearing.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Phylogeny and architecture of TRP channels.
Figure 2: Activation range of human and Drosophila thermoTRPs.
Figure 3: Temperature sensitivity is voltage dependent.
Figure 5: Gating kinetics of cold- and heat-activated thermoTRPs.
Figure 4: Converting mechanical energy into channel gating.

Similar content being viewed by others

References

  1. Hille, B. Ion channels of Excitable Membranes (Sinauer Associates, Sunderland, Massachusetts, 2001).

    Google Scholar 

  2. MacKinnon, R. Potassium channels and the atomic basis of selective ion conduction (Nobel Lecture). Angew. Chem. Int. Edn Engl. 43, 4265–4277 (2004).

    Article  CAS  Google Scholar 

  3. Cosens, D.J. & Manning, A. Abnormal electroretinogram from a Drosophila mutant. Nature 224, 285–287 (1969).

    Article  CAS  PubMed  Google Scholar 

  4. Montell, C. & Rubin, G.M. Molecular characterization of the Drosophila trp locus: a putative integral membrane protein required for phototransduction. Neuron 2, 1313–1323 (1989).

    Article  CAS  PubMed  Google Scholar 

  5. Hardie, R.C. & Minke, B. The trp gene is essential for a light-activated Ca2+ channel in Drosophila photoreceptors. Neuron 8, 643–651 (1992).

    Article  CAS  PubMed  Google Scholar 

  6. Phillips, A.M., Bull, A. & Kelly, L.E. Identification of a Drosophila gene encoding a calmodulin-binding protein with homology to the trp phototransduction gene. Neuron 8, 631–642 (1992).

    Article  CAS  PubMed  Google Scholar 

  7. Xu, X.Z., Chien, F., Butler, A., Salkoff, L. & Montell, C. TRPgamma, a Drosophila TRP-related subunit, forms a regulated cation channel with TRPL. Neuron 26, 647–657 (2000).

    Article  CAS  PubMed  Google Scholar 

  8. Reuss, H., Mojet, M.H., Chyb, S. & Hardie, R.C. In vivo analysis of the Drosophila light-sensitive channels, TRP and TRPL. Neuron 19, 1249–1259 (1997).

    Article  CAS  PubMed  Google Scholar 

  9. Hardie, R.C. & Raghu, P. Visual transduction in Drosophila. Nature 413, 186–193 (2001).

    Article  CAS  PubMed  Google Scholar 

  10. Chyb, S., Raghu, P. & Hardie, R.C. Polyunsaturated fatty acids activate the Drosophila light-sensitive channels TRP and TRPL. Nature 397, 255–259 (1999).

    Article  CAS  PubMed  Google Scholar 

  11. Petersen, C.C., Berridge, M.J., Borgese, M.F. & Bennett, D.L. Putative capacitative calcium entry channels: expression of Drosophila trp and evidence for the existence of vertebrate homologues. Biochem. J. 311, 41–44 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Wes, P.D. et al. TRPC1, a human homolog of a Drosophila store-operated channel. Proc. Natl. Acad. Sci. USA 92, 9652–9656 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Vriens, J., Owsianik, G., Voets, T., Droogmans, G. & Nilius, B. Invertebrate TRP proteins as functional models for mammalian channels. Pflugers Arch. 449, 213–226 (2004).

    CAS  PubMed  Google Scholar 

  14. Montell, C. The TRP superfamily of cation channels. Sci. STKE 2005, re3 (2005).

    PubMed  Google Scholar 

  15. Clapham, D.E. TRP channels as cellular sensors. Nature 426, 517–524 (2003).

    Article  CAS  PubMed  Google Scholar 

  16. Yellen, G. The voltage-gated potassium channels and their relatives. Nature 419, 35–42 (2002).

    Article  CAS  PubMed  Google Scholar 

  17. Hoenderop, J.G. et al. Homo- and heterotetrameric architecture of the epithelial Ca2+ channels, TRPV5 and TRPV6. EMBO J. 22, 776–785 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Voets, T., Janssens, A., Droogmans, G. & Nilius, B. Outer pore architecture of a Ca2+-selective TRP channel. J. Biol. Chem. 279, 15223–15230 (2004).

    Article  CAS  PubMed  Google Scholar 

  19. Fleig, A. & Penner, R. The TRPM ion channel subfamily: molecular, biophysical and functional features. Trends Pharmacol. Sci. 25, 633–639 (2004).

    Article  CAS  PubMed  Google Scholar 

  20. Birnbaumer, L. et al. On the molecular basis and regulation of cellular capacitative calcium entry: roles for Trp proteins. Proc. Natl. Acad. Sci. USA 93, 15195–15202 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Clapham, D.E. TRP is cracked but is CRAC TRP? Neuron 16, 1069–1072 (1996).

    Article  CAS  PubMed  Google Scholar 

  22. Zhu, X. et al. trp, a novel mammalian gene family essential for agonist-activated capacitative Ca2+ entry. Cell 85, 661–671 (1996).

    Article  CAS  PubMed  Google Scholar 

  23. Zitt, C. et al. Cloning and functional expression of a human Ca2+-permeable cation channel activated by calcium store depletion. Neuron 16, 1189–1196 (1996).

    Article  CAS  PubMed  Google Scholar 

  24. Caterina, M.J. et al. The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 389, 816–824 (1997).

    Article  CAS  PubMed  Google Scholar 

  25. Montell, C. et al. A unified nomenclature for the superfamily of TRP cation channels. Mol. Cell 9, 229–231 (2002).

    Article  CAS  PubMed  Google Scholar 

  26. Patapoutian, A., Peier, A.M., Story, G.M. & Viswanath, V. ThermoTRP channels and beyond: mechanisms of temperature sensation. Nat. Rev. Neurosci. 4, 529–539 (2003).

    Article  CAS  PubMed  Google Scholar 

  27. Caterina, M.J., Rosen, T.A., Tominaga, M., Brake, A.J. & Julius, D. A capsaicin-receptor homologue with a high threshold for noxious heat. Nature 398, 436–441 (1999).

    Article  CAS  PubMed  Google Scholar 

  28. Xu, H. et al. TRPV3 is a calcium-permeable temperature-sensitive cation channel. Nature 418, 181–186 (2002).

    Article  CAS  PubMed  Google Scholar 

  29. Peier, A.M. et al. A heat-sensitive TRP channel expressed in keratinocytes. Science 296, 2046–2049 (2002).

    Article  CAS  PubMed  Google Scholar 

  30. Smith, G.D. et al. TRPV3 is a temperature-sensitive vanilloid receptor-like protein. Nature 418, 186–190 (2002).

    Article  CAS  PubMed  Google Scholar 

  31. Güler, A.D. et al. Heat-evoked activation of the ion channel, TRPV4. J. Neurosci. 22, 6408–6414 (2002).

    Article  PubMed  PubMed Central  Google Scholar 

  32. Watanabe, H. et al. Heat-evoked activation of TRPV4 channels in a HEK293 cell expression system and in native mouse aorta endothelial cells. J. Biol. Chem. 277, 47044–47051 (2002).

    Article  CAS  PubMed  Google Scholar 

  33. McKemy, D.D., Neuhäusser, W.M. & Julius, D. Identification of a cold receptor reveals a general role for TRP channels in thermosensation. Nature 416, 52–58 (2002).

    Article  CAS  PubMed  Google Scholar 

  34. Peier, A.M. et al. A TRP channel that senses cold stimuli and menthol. Cell 108, 705–715 (2002).

    Article  CAS  PubMed  Google Scholar 

  35. Story, G.M. et al. ANKTM1, a TRP-like channel expressed in nociceptive neurons, is activated by cold temperatures. Cell 112, 819–829 (2003).

    Article  CAS  PubMed  Google Scholar 

  36. Jordt, S.E. et al. Mustard oils and cannabinoids excite sensory nerve fibres through the TRP channel ANKTM1. Nature 427, 260–265 (2004).

    Article  CAS  PubMed  Google Scholar 

  37. Prescott, E.D. & Julius, D. A modular PIP2 binding site as a determinant of capsaicin receptor sensitivity. Science 300, 1284–1288 (2003).

    Article  CAS  PubMed  Google Scholar 

  38. Chuang, H.H. et al. Bradykinin and nerve growth factor release the capsaicin receptor from PtdIns(4,5)P2-mediated inhibition. Nature 411, 957–962 (2001).

    Article  CAS  PubMed  Google Scholar 

  39. Liu, B. & Qin, F. Functional control of cold- and menthol-sensitive TRPM8 ion channels by phosphatidylinositol 4,5-bisphosphate. J. Neurosci. 25, 1674–1681 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Rohacs, T., Lopes, C.M., Michailidis, I. & Logothetis, D.E. PI(4,5)P(2) regulates the activation and desensitization of TRPM8 channels through the TRP domain. Nat. Neurosci. 8, 626–634 (2005).

    Article  CAS  PubMed  Google Scholar 

  41. Voets, T. et al. The principle of temperature-dependent gating in cold- and heat-sensitive TRP channels. Nature 430, 748–754 (2004).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Caterina, M.J. et al. Impaired nociception and pain sensation in mice lacking the capsaicin receptor. Science 288, 306–313 (2000).

    Article  CAS  PubMed  Google Scholar 

  44. Davis, J.B. et al. Vanilloid receptor-1 is essential for inflammatory thermal hyperalgesia. Nature 405, 183–187 (2000).

    Article  CAS  PubMed  Google Scholar 

  45. Moqrich, A. et al. Impaired thermosensation in mice lacking TRPV3, a heat and camphor sensor in the skin. Science 307, 1468–1472 (2005).

    Article  CAS  PubMed  Google Scholar 

  46. Lee, H., Iida, T., Mizuno, A., Suzuki, M. & Caterina, M.J. Altered thermal selection behavior in mice lacking transient receptor potential vanilloid 4. J. Neurosci. 25, 1304–1310 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Tracey, W.D., Jr, Wilson, R.I., Laurent, G. & Benzer, S. painless, a Drosophila gene essential for nociception. Cell 113, 261–273 (2003).

    Article  CAS  PubMed  Google Scholar 

  48. Lee, Y. et al. Pyrexia is a new thermal transient receptor potential channel endowing tolerance to high temperatures in Drosophila melanogaster. Nat. Genet. 37, 305–310 (2005).

    Article  CAS  PubMed  Google Scholar 

  49. Rosenzweig, M. et al. The Drosophila ortholog of vertebrate TRPA1 regulates thermotaxis. Genes Dev. 19, 419–424 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Viswanath, V. et al. Opposite thermosensor in fruitfly and mouse. Nature 423, 822–823 (2003).

    Article  CAS  PubMed  Google Scholar 

  51. Bandell, M. et al. Noxious cold ion channel TRPA1 is activated by pungent compounds and bradykinin. Neuron 41, 849–857 (2004).

    Article  CAS  PubMed  Google Scholar 

  52. Szallasi, A., Blumberg, P.M., Annicelli, L.L., Krause, J.E. & Cortright, D.N. The cloned rat vanilloid receptor VR1 mediates both R-type binding and C-type calcium response in dorsal root ganglion neurons. Mol. Pharmacol. 56, 581–587 (1999).

    Article  CAS  PubMed  Google Scholar 

  53. McNamara, F.N., Randall, A. & Gunthorpe, M.J. Effects of piperine, the pungent component of black pepper, at the human vanilloid receptor (TRPV1). Br. J. Pharmacol. 144, 781–790 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Macpherson, L. et al. The pungency of garlic: activation of TRPA1 and TRPV1 in response to allicin. Curr. Biol. 15, 929–934 (2005).

    Article  CAS  PubMed  Google Scholar 

  55. Watanabe, H. et al. Activation of TRPV4 channels (hVRL-2/mTRP12) by phorbol derivatives. J. Biol. Chem. 277, 13569–13577 (2002).

    Article  CAS  PubMed  Google Scholar 

  56. Chuang, H.H., Neuhausser, W.M. & Julius, D. The super-cooling agent icilin reveals a mechanism of coincidence detection by a temperature-sensitive TRP channel. Neuron 43, 859–869 (2004).

    Article  CAS  PubMed  Google Scholar 

  57. Zygmunt, P.M. et al. Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide. Nature 400, 452–457 (1999).

    Article  CAS  PubMed  Google Scholar 

  58. Hwang, S.W. et al. Direct activation of capsaicin receptors by products of lipoxygenases: endogenous capsaicin-like substances. Proc. Natl. Acad. Sci. USA 97, 6155–6160 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Watanabe, H. et al. Anandamide and arachidonic acid use epoxyeicosatrienoic acids to activate TRPV4 channels. Nature 424, 434–438 (2003).

    Article  CAS  PubMed  Google Scholar 

  60. Jordt, S.E. & Julius, D. Molecular basis for species-specific sensitivity to “hot” chili peppers. Cell 108, 421–430 (2002).

    Article  CAS  PubMed  Google Scholar 

  61. Jung, J. et al. Agonist recognition sites in the cytosolic tails of vanilloid receptor 1. J. Biol. Chem. 277, 44448–44454 (2002).

    Article  CAS  PubMed  Google Scholar 

  62. Vriens, J. et al. Cell swelling, heat, and chemical agonists use distinct pathways for the activation of the cation channel TRPV4. Proc. Natl. Acad. Sci. USA 101, 396–401 (2004).

    Article  CAS  PubMed  Google Scholar 

  63. Colbert, H.A., Smith, T.L. & Bargmann, C.I. OSM-9, a novel protein with structural similarity to channels, is required for olfaction, mechanosensation, and olfactory adaptation in Caenorhabditis elegans. J. Neurosci. 17, 8259–8269 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Liedtke, W. et al. Vanilloid receptor-related osmotically activated channel (VR-OAC), a candidate vertebrate osmoreceptor. Cell 103, 525–535 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Strotmann, R., Harteneck, C., Nunnenmacher, K., Schultz, G. & Plant, T.D. OTRPC4, a nonselective cation channel that confers sensitivity to extracellular osmolarity. Nat. Cell Biol. 2, 695–702 (2000).

    Article  CAS  PubMed  Google Scholar 

  66. Wissenbach, U., Bodding, M., Freichel, M. & Flockerzi, V. Trp12, a novel Trp related protein from kidney. FEBS Lett. 485, 127–134 (2000).

    Article  CAS  PubMed  Google Scholar 

  67. Suzuki, M., Mizuno, A., Kodaira, K. & Imai, M. Impaired pressure sensation in mice lacking TRPV4. J. Biol. Chem. 278, 22664–22668 (2003).

    Article  CAS  PubMed  Google Scholar 

  68. Mizuno, A., Matsumoto, N., Imai, M. & Suzuki, M. Impaired osmotic sensation in mice lacking TRPV4. Am J. Physiol. Cell Physiol. 285, C96–101 (2003).

    Article  CAS  PubMed  Google Scholar 

  69. Liedtke, W. & Friedman, J.M. Abnormal osmotic regulation in trpv4−/− mice. Proc. Natl. Acad. Sci. USA 100, 13698–13703 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Liedtke, W., Tobin, D.M., Bargmann, C.I. & Friedman, J.M. Mammalian TRPV4 (VR-OAC) directs behavioral responses to osmotic and mechanical stimuli in Caenorhabditis elegans. Proc. Natl. Acad. Sci. USA 100, 14531–14536 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Muraki, K. et al. TRPV2 is a component of osmotically sensitive cation channels in murine aortic myocytes. Circ. Res. 93, 829–838 (2003).

    Article  CAS  PubMed  Google Scholar 

  72. Grimm, C., Kraft, R., Sauerbruch, S., Schultz, G. & Harteneck, C. Molecular and functional characterization of the melastatin-related cation channel TRPM3. J. Biol. Chem. 278, 21493–21501 (2003).

    Article  CAS  PubMed  Google Scholar 

  73. Kim, J. et al. A TRPV family ion channel required for hearing in Drosophila. Nature 424, 81–84 (2003).

    Article  CAS  PubMed  Google Scholar 

  74. Maroto, R. et al. TRPC1 forms the stretch-activated cation channel in vertebrate cells. Nat. Cell Biol. 7, 179–185 (2005).

    Article  CAS  PubMed  Google Scholar 

  75. Walker, R.G., Willingham, A.T. & Zuker, C.S. A Drosophila mechanosensory transduction channel. Science 287, 2229–2234 (2000).

    Article  CAS  PubMed  Google Scholar 

  76. Sidi, S., Friedrich, R.W. & Nicolson, T. NompC TRP channel required for vertebrate sensory hair cell mechanotransduction. Science 301, 96–99 (2003).

    Article  CAS  PubMed  Google Scholar 

  77. Nauli, S.M. et al. Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells. Nat. Genet. 33, 129–137 (2003).

    Article  CAS  PubMed  Google Scholar 

  78. Koulen, P. et al. Polycystin-2 is an intracellular calcium release channel. Nat. Cell Biol. 4, 191–197 (2002).

    Article  CAS  PubMed  Google Scholar 

  79. Corey, D.P. et al. TRPA1 is a candidate for the mechanosensitive transduction channel of vertebrate hair cells. Nature 432, 723–730 (2004).

    Article  CAS  PubMed  Google Scholar 

  80. Perozo, E., Cortes, D.M., Sompornpisut, P., Kloda, A. & Martinac, B. Open channel structure of MscL and the gating mechanism of mechanosensitive channels. Nature 418, 942–948 (2002).

    Article  CAS  PubMed  Google Scholar 

  81. Sotomayor, M., Corey, D.P. & Schulten, K. In search of the hair-cell gating spring elastic properties of ankyrin and cadherin repeats. Structure 13, 669–682 (2005).

    Article  CAS  PubMed  Google Scholar 

  82. Howard, J. & Bechstedt, S. Hypothesis: a helix of ankyrin repeats of the NOMPC-TRP ion channel is the gating spring of mechanoreceptors. Curr. Biol. 14, R224–R226 (2004).

    Article  CAS  PubMed  Google Scholar 

  83. Neher, E. Molecular biology meets microelectronics. Nat. Biotechnol. 19, 114 (2001).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Research in the authors' laboratory is supported by the Human Frontiers Science Programme (HFSP Research Grant Ref. RGP 32/2004), the Belgian Federal Government, the Flemish Government and the Onderzoeksraad KU Leuven (GOA 2004/07, FWO G.0214.99, FWO G.0136.00, FWO G.0172.03, and the Interuniversity Poles of Attraction program, Prime Minister's Office IUAP).

Author information

Authors and Affiliations

  1. Laboratory of Physiology, Campus Gasthuisberg O&N, KU Leuven, Leuven, B-3000, Belgium

    Thomas Voets, Karel Talavera, Grzegorz Owsianik & Bernd Nilius

Authors
  1. Thomas Voets
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Karel Talavera
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Grzegorz Owsianik
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bernd Nilius
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Thomas Voets.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Voets, T., Talavera, K., Owsianik, G. et al. Sensing with TRP channels. Nat Chem Biol 1, 85–92 (2005). https://doi.org/10.1038/nchembio0705-85

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nchembio0705-85

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing