Voltage Sensing in Thermo-TRP Channels

  • Sebastian Brauchi
  • Patricio Orio
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 704)


Membrane voltage, ligand binding, mechanical force and temperature can all induce conformational changes that open ion channel pores. A key question in understanding ion channel function is how the protein domains involved in sensing stimuli (sensors) communicate with the pore to gate its opening and closing. TRP channels are considered six-transmembrane cation-permeable channels, distant relatives of voltage-gated potassium channels (Kv), which are known to be activated by membrane depolarization. Understanding the molecular nature of thermo-TRP channel gating offers a fair challenge to biophysicists. This chapter will summarize our present knowledge on the effect of voltage and temperature during thermo-TRP channel activation.


TRP channels Voltage activation Temperature Voltage sensor Thermo-TRP TRPM8 TRPV1 Allosteric models Polymodal activation Thermodynamics 



SB work is funded by FONDECYT grant 11070190. PO work is funded by FONDECYT 11090308 and DIPUV 51/2007 (U. de Valparaiso) grants. We thank Dr. H. Kurata for his critical reading of the manuscript.


  1. 1.
    Ramsey IS, Delling M, Clapham DE (2006) An introduction to TRP channels. Annu Rev Physiol 68:619–647CrossRefPubMedGoogle Scholar
  2. 2.
    Latorre R, Brauchi S, Orta G, Zaelzer C, Vargas G (2007) Thermo TRP channels as modular proteins with allosteric gating. Cell Calcium 42:427–438CrossRefPubMedGoogle Scholar
  3. 3.
    Latorre R, Zaelzer C, Brauchi S (2009) Structure-functional intimacies of transient receptor potential channels. Q Rev Biophys 42:201–246CrossRefPubMedGoogle Scholar
  4. 4.
    Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D (1997) The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 389: 816–824CrossRefPubMedGoogle Scholar
  5. 5.
    Hodgkin AL, Huxley AF (1952) A quantitative description of membrane current and itsapplication to conduction and excitation in nerve. J Physiol 117:500–544CrossRefPubMedCentralPubMedGoogle Scholar
  6. 6.
    Bezanilla F (2000) The voltage sensor in voltage-dependent ion channels. Physiol Rev 80:555–592PubMedGoogle Scholar
  7. 7.
    Long SB, Tao X, Campbell EB, MacKinnon R (2007) Atomic structure of a voltage-dependent k+ channel in a lipid membrane-like environment. Nature 450:376–382CrossRefPubMedGoogle Scholar
  8. 8.
    Noda M, Shimizu S, Tanabe T, Takai T, Kayano T, Ikeda T, Takahashi H, Nakayama H, Kanaoka Y, Minamino N et al (1984) Primary structure of electrophorus electricus sodium channel deduced from cDNA sequence. Nature 312:121–127CrossRefPubMedGoogle Scholar
  9. 9.
    Seoh SA, Sigg D, Papazian DM, Bezanilla F (1996) Voltage-sensing residues in the S2 and S4 segments of the shaker k+ channel. Neuron 16:1159–1167CrossRefPubMedGoogle Scholar
  10. 10.
    Jiang Y, Lee A, Chen J, Ruta V, Cadene M, Chait BT, Mackinnon R (2003) X-ray structure of a voltage-dependent k channel. Nature 423:33–41CrossRefPubMedGoogle Scholar
  11. 11.
    Swartz KJ (2008) Sensing voltage across lipid membranes. Nature 456:891–897CrossRefPubMedCentralPubMedGoogle Scholar
  12. 12.
    Murata Y, Iwasaki H, Sasaki M, Inaba K, Okamura Y (2005) Phosphoinositide phosphatase activity coupled to an intrinsic voltage sensor. Nature 435:1239–1243CrossRefPubMedGoogle Scholar
  13. 13.
    Sasaki M, Takagi M, Okamura Y (2006) A voltage sensor-domain protein is a voltage-gated proton channel. Science 312:589–592CrossRefPubMedGoogle Scholar
  14. 14.
    Ramsey IS, Moran MM, Chong JA, Clapham DE (2006) A voltage-gated proton-selective channel lacking the pore domain. Nature 440:1213–1216CrossRefPubMedCentralPubMedGoogle Scholar
  15. 15.
    Armstrong CM, Bezanilla F (1973) Currents related to movement of the gating particles of the sodium channels. Nature 242:459–461CrossRefPubMedGoogle Scholar
  16. 16.
    Schneider MF, Chandler WK (1973) Voltage dependent charge movement of skeletal muscle: a possible step in excitation-contraction coupling. Nature 242:244–246CrossRefPubMedGoogle Scholar
  17. 17.
    Schoppa NE, McCormack K, Tanouye MA, Sigworth FJ (1992) The size of gating charge in wild-type and mutant shaker potassium channels. Science (80) 255:1712–1715Google Scholar
  18. 18.
    Sigg D, Bezanilla F (1997) Total charge movement per channel. the relation between gating charge displacement and the voltage sensitivity of activation. J Gen Physiol 109: 27–39CrossRefPubMedCentralPubMedGoogle Scholar
  19. 19.
    Aggarwal SK, MacKinnon R (1996) Contribution of the S4 segment to gating charge in the shaker K+ channel. Neuron 16:1169–1177CrossRefPubMedGoogle Scholar
  20. 20.
    Voets T, Droogmans G, Wissenbach U, Janssens A, Flockerzi V, Nilius B (2004) The principle of temperature-dependent gating in cold- and heat-sensitive TRP channels. Nature 430:748–754CrossRefPubMedGoogle Scholar
  21. 21.
    Brauchi S, Orio P, Latorre R (2004) Clues to understanding cold sensation: thermodynamics and electrophysiological analysis of the cold receptor trpm8. Proc Natl Acad Sci USA 101:15494–15499CrossRefPubMedCentralPubMedGoogle Scholar
  22. 22.
    Karashima Y, Talavera K, Everaerts W, Janssens A, Kwan KY, Vennekens R, Nilius B, Voets T (2009) TRPA1 acts as a cold sensor in vitro and in vivo. Proc Natl Acad Sci USA 106:1273–1278CrossRefPubMedCentralPubMedGoogle Scholar
  23. 23.
    Latorre R, Vargas G, Orta G, Brauchi S (2007) Voltage and temperature gating of thermoTRP channels. In: Liedtke W, Heller S (eds) TRP ion channels function in sensory transduction and cellular signaling cascades. CRC Taylor & Francis, London, pp 287–302Google Scholar
  24. 24.
    Gaudet R (2008) P channels entering the structural era. J Physiol 586:3565–3575CrossRefPubMedCentralPubMedGoogle Scholar
  25. 25.
    Moiseenkova-bell VY, Stanciu LA, Serysheva II, Tobe BJ, Wensel TG (2008) Structure of TRPV1 channel revealed by electron cryomicroscopy. Proc Natl Acad Sci USA 105:7451–7455CrossRefPubMedCentralPubMedGoogle Scholar
  26. 26.
    Almers W (1978) Gating currents and charge movements in excitable membranes. Rev Physiol Biochem Pharmacol 82:96–190CrossRefPubMedGoogle Scholar
  27. 27.
    Voets T, Owsianik G, Janssens A, Talavera K, Nilius B (2007) TRPM8 voltage sensor mutants reveal a mechanism for integrating thermal and chemical stimuli. Nat Chem Biol 3:174–182CrossRefPubMedGoogle Scholar
  28. 28.
    Liu B, Hui K, Qin F (2003) Thermodynamics of heat activation of single capsaicin ion channels vr1. Biophys J 85:2988–3006CrossRefPubMedCentralPubMedGoogle Scholar
  29. 29.
    Iggo A (1969) Cutaneous thermoreceptors in primates and sub-primates. J Physiol 200: 403–430CrossRefPubMedCentralPubMedGoogle Scholar
  30. 30.
    Lecar H, Ehrenstein G, Latorre R (1975) Mechanism for channel gating in excitable bilayers. Ann NY Acad Sci 264:304–313CrossRefPubMedGoogle Scholar
  31. 31.
    Yang F, Cui Y, Wang K, Zheng J (2010) Thermosensitive trp channel pore turret is part of the temperature activation pathway. Proc Natl Acad Sci USA 107:7083–7088CrossRefPubMedCentralPubMedGoogle Scholar
  32. 32.
    Privalov PL (1989) Thermodynamic problems of protein structure. Annu Rev Biophys Chem 18:47–69CrossRefGoogle Scholar
  33. 33.
    Privalov PL. Thermodynamics of protein folding. 1997; 447–474Google Scholar
  34. 34.
    Gursky O, Atkinson D (1996) High- and low-temperature unfolding of human high-density apolipoprotein a-2. Protein Sci 5:1874–1882CrossRefPubMedCentralPubMedGoogle Scholar
  35. 35.
    Privalov PL, Griko YV, Venyaminov S, Kutyshenko VP (1986) Cold denaturation of myoglobin. J Mol Biol 190:487–498CrossRefPubMedGoogle Scholar
  36. 36.
    Griko YV, Venyaminov S, Privalov PL (1989) Heat and cold denaturation of phosphoglycerate kinase (interaction of domains). FEBS Lett 244:276–278CrossRefPubMedGoogle Scholar
  37. 37.
    Myers BR, Bohlen CJ, Julius D (2008) A yeast genetic screen reveals a critical role for the pore helix domain in TRP channel gating. Neuron 58:362–373CrossRefPubMedCentralPubMedGoogle Scholar
  38. 38.
    Grandl J, Hu H, Bandell M, Bursulaya B, Schmidt M, Petrus M, Patapoutian A (2008) Pore region of TRPV3 ion channel is specifically required for heat activation. Nat Neurosci 11:1007–1013CrossRefPubMedCentralPubMedGoogle Scholar
  39. 39.
    Grandl J, Kim SE, Uzzell V, Bursulaya B, Petrus M, Bandell M, Patapoutian A (2010) Temperature-induced opening of TRPV1 ion channel is stabilized by the pore domain. Nat Neurosci 6:708–714CrossRefGoogle Scholar
  40. 40.
    Brauchi S, Orta G, Mascayano C, Salazar M, Raddatz N, Urbina H, Rosenmann E, Gonzalez-Nilo F, Latorre R (2007) Dissection of the components for pip2 activation and thermosensation in trp channels. Proc Natl Acad Sci USA 104:10246–10251CrossRefPubMedCentralPubMedGoogle Scholar
  41. 41.
    Yellen G (1998) The moving parts of voltage-gated ion channels. Quart Rev Biophys 31:239–295CrossRefGoogle Scholar
  42. 42.
    Matta JA, Ahern GP (2007) Voltage is a partial activator of rat thermosensitive TRP channels. J Physiol 585:469–482CrossRefPubMedCentralPubMedGoogle Scholar
  43. 43.
    Altomare C, Bucchi A, Camatini E, Baruscotti M, Viscomi C, Moroni A, DiFrancesco D (2001) Integrated allosteric model of voltage gating of HCN channels. J Gen Physiol 117:519–532CrossRefPubMedCentralPubMedGoogle Scholar
  44. 44.
    Horrigan FT, Aldrich RW (2002) Coupling between voltage sensor activation, Ca2+ binding and channel opening in large conductance (BK) potassium channels. J Gen Physiol 120: 267–305CrossRefPubMedCentralPubMedGoogle Scholar
  45. 45.
    Horrigan FT, Cui J, Aldrich RW (1999) Allosteric voltage gating of potassium channels i. mslo ionic currents in the absence of Ca2+. J Gen Physiol 114:277–304CrossRefPubMedCentralPubMedGoogle Scholar
  46. 46.
    Colquhoun D, Hawkes AG (1981) On the stochastic properties of single ion channels. Proc R Soc Lond B Biol Sci 211:205–235CrossRefPubMedGoogle Scholar
  47. 47.
    Lu Z, Klem AM, Ramu Y (2002) Coupling between voltage sensors and activation gate in voltage-gated K+ channels. J Gen Physiol 120:663–676CrossRefPubMedCentralPubMedGoogle Scholar
  48. 48.
    Yao J, Liu B, Qin F (2010) Pore turret of thermal TRP channels is not essential for temperature sensing. Proc Natl Acad Sci USA 107(32):E125CrossRefPubMedCentralPubMedGoogle Scholar
  49. 49.
    Yang F, Ciu Y, Wang K, Zheng J (2010) Reply to Yao et al.: is the pore turret just thermoTRP channels’ appendix? Proc Natl Acad Sci USA 107(32):E126–E127CrossRefPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  1. 1.Facultad de MedicinaInstituto de Fisiologia, Universidad Austral de ChileValdiviaChile
  2. 2.Centro Interdisciplinario de Neurociencia de Valparaíso (CINV)Facultad de Ciencias, Universidad de ValparaísoValparaísoChile

Personalised recommendations