TRPs et al.: a molecular toolkit for thermosensory adaptations

  • Lydia J. Hoffstaetter
  • Sviatoslav N. Bagriantsev
  • Elena O. Gracheva
Invited Review

Abstract

The ability to sense temperature is crucial for the survival of an organism. Temperature influences all biological operations, from rates of metabolic reactions to protein folding, and broad behavioral functions, from feeding to breeding, and other seasonal activities. The evolution of specialized thermosensory adaptations has enabled animals to inhabit extreme temperature niches and to perform specific temperature-dependent behaviors. The function of sensory neurons depends on the participation of various types of ion channels. Each of the channels involved in neuronal excitability, whether through the generation of receptor potential, action potential, or the maintenance of the resting potential have temperature-dependent properties that can tune the neuron’s response to temperature stimuli. Since the function of all proteins is affected by temperature, animals need adaptations not only for detecting different temperatures, but also for maintaining sensory ability at different temperatures. A full understanding of the molecular mechanism of thermosensation requires an investigation of all channel types at each step of thermosensory transduction. A fruitful avenue of investigation into how different molecules can contribute to the fine-tuning of temperature sensitivity is to study the specialized adaptations of various species. Given the diversity of molecular participants at each stage of sensory transduction, animals have a toolkit of channels at their disposal to adapt their thermosensitivity to their particular habitats or behavioral circumstances.

Keywords

Thermosensation Molecular adaptations Ion channels TRP channels Neuronal excitability 

Notes

Acknowledgements

We would like to thank Jeremy Borjon for his careful reading of this manuscript.

Funding information

This study was partly funded by fellowships from the Beckman Foundation, Rita Allen Foundation and National Institute of Health grant 1R01NS091300-01A1 to E.O.G; by American Heart Association grant 14SDG17880015 and National Science Foundation grant 1453167 to S.N.B; and L.J.H was supported by the National Institute of Health training grant 5 T32 HG003198.

References

  1. 1.
    Abuin L, Bargeton B, Ulbrich MH, Isacoff EY, Kellenberger S, Benton R (2011) Functional architecture of olfactory ionotropic glutamate receptors. Neuron 69:44–60PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    Acosta C, Djouhri L, Watkins R, Berry C, Bromage K, Lawson SN (2014) TREK2 expressed selectively in IB4-binding C-fiber nociceptors hyperpolarizes their membrane potentials and limits spontaneous pain. J Neurosci: Off J Soc Neurosci 34:1494–1509CrossRefGoogle Scholar
  3. 3.
    Ahluwalia J, Rang H, Nagy I (2002) The putative role of vanilloid receptor-like protein-1 in mediating high threshold noxious heat-sensitivity in rat cultured primary sensory neurons. Eur J Neurosci 16:1483–1489PubMedCrossRefGoogle Scholar
  4. 4.
    Akopian AN, Sivilotti L, Wood JN (1996) A tetrodotoxin-resistant voltage-gated sodium channel expressed by sensory neurons. Nature 379:257–262PubMedCrossRefGoogle Scholar
  5. 5.
    Al-Anzi B, Tracey WD Jr, Benzer S (2006) Response of drosophila to wasabi is mediated by painless, the fly homolog of mammalian TRPA1/ANKTM1. Curr Biol: CB 16:1034–1040PubMedCrossRefGoogle Scholar
  6. 6.
    Alloui A, Zimmermann K, Mamet J, Duprat F, Noel J, Chemin J, Guy N, Blondeau N, Voilley N, Rubat-Coudert C, Borsotto M, Romey G, Heurteaux C, Reeh P, Eschalier A, Lazdunski M (2006) TREK-1, a K+ channel involved in polymodal pain perception. EMBO J 25:2368–2376PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Amaya F, Decosterd I, Samad TA, Plumpton C, Tate S, Mannion RJ, Costigan M, Woolf CJ (2000) Diversity of expression of the sensory neuron-specific TTX-resistant voltage-gated sodium ion channels SNS and SNS2. Mol Cell Neurosci 15:331–342PubMedCrossRefGoogle Scholar
  8. 8.
    Aoki I, Mori I (2015) Molecular biology of thermosensory transduction in C. elegans. Curr Opin Neurobiol 34:117–124PubMedCrossRefGoogle Scholar
  9. 9.
    Arenas OM, Zaharieva EE, Para A, Vásquez-Doorman C, Petersen CP, Gallio M (2017) Activation of planarian TRPA1 by reactive oxygen species reveals a conserved mechanism for animal nociception. Nat Neurosci 20:1686–1693PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Askwith CC, Benson CJ, Welsh MJ, Snyder PM (2001) DEG/ENaC ion channels involved in sensory transduction are modulated by cold temperature. Proc Natl Acad Sci U S A 98:6459–6463PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Bagriantsev SN, Clark KA, Minor DL Jr (2012) Metabolic and thermal stimuli control K(2P)2.1 (TREK-1) through modular sensory and gating domains. EMBO J 31:3297–3308PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Bagriantsev SN, Peyronnet R, Clark KA, Honore E, Minor DL Jr (2011) Multiple modalities converge on a common gate to control K2P channel function. EMBO J 30:3594–3606PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Bandell M, Story GM, Hwang SW, Viswanath V, Eid SR, Petrus MJ, Earley TJ, Patapoutian A (2004) Noxious cold ion channel TRPA1 is activated by pungent compounds and bradykinin. Neuron 41:849–857PubMedCrossRefGoogle Scholar
  14. 14.
    Bang H, Kim Y, Kim D (2000) TREK-2, a new member of the mechanosensitive tandem-pore K+ channel family. J Biol Chem 275:17412–17419PubMedCrossRefGoogle Scholar
  15. 15.
    Barger JL, Barnes BM, Boyer BB (2006) Regulation of UCP1 and UCP3 in arctic ground squirrels and relation with mitochondrial proton leak. J Appl Physiol (Bethesda, Md: 1985) 101:339–347CrossRefGoogle Scholar
  16. 16.
    Bautista DM, Movahed P, Hinman A, Axelsson HE, Sterner O, Hogestatt ED, Julius D, Jordt SE, Zygmunt PM (2005) Pungent products from garlic activate the sensory ion channel TRPA1. Proc Natl Acad Sci U S A 102:12248–12252PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Bautista DM, Siemens J, Glazer JM, Tsuruda PR, Basbaum AI, Stucky CL, Jordt SE, Julius D (2007) The menthol receptor TRPM8 is the principal detector of environmental cold. Nature 448:204–208PubMedCrossRefGoogle Scholar
  18. 18.
    Benarroch EE (2015) Ion channels in nociceptors: recent developments. Neurology 84:1153–1164PubMedCrossRefGoogle Scholar
  19. 19.
    Bennett DL, Woods CG (2014) Painful and painless channelopathies. Lancet Neurol 13:587–599PubMedCrossRefGoogle Scholar
  20. 20.
    Blasius AL, Dubin AE, Petrus MJ, Lim BK, Narezkina A, Criado JR, Wills DN, Xia Y, Moresco EM, Ehlers C, Knowlton KU, Patapoutian A, Beutler B (2011) Hypermorphic mutation of the voltage-gated sodium channel encoding gene Scn10a causes a dramatic stimulus-dependent neurobehavioral phenotype. Proc Natl Acad Sci U S A 108:19413–19418PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Casterlin ME, Reynolds WW (1980) Diel activity and thermoregulatory behavior of a fully aquatic frog: Xenopus laevis. Hydrobiologia 75:189–191CrossRefGoogle Scholar
  22. 22.
    Caterina MJ, Leffler A, Malmberg AB, Martin WJ, Trafton J, Petersen-Zeitz KR, Koltzenburg M, Basbaum AI, Julius D (2000) Impaired nociception and pain sensation in mice lacking the capsaicin receptor. Science (New York, NY) 288:306–313CrossRefGoogle Scholar
  23. 23.
    Caterina MJ, Rosen TA, Tominaga M, Brake AJ, Julius D (1999) A capsaicin-receptor homologue with a high threshold for noxious heat. Nature 398:436–441PubMedCrossRefGoogle Scholar
  24. 24.
    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 389:816–824PubMedCrossRefGoogle Scholar
  25. 25.
    Catterall WA, Goldin AL, Waxman SG (2005) International Union of Pharmacology. XLVII. Nomenclature and structure-function relationships of voltage-gated sodium channels. Pharmacol Rev 57:397–409PubMedCrossRefGoogle Scholar
  26. 26.
    Cavanaugh EJ, Simkin D, Kim D (2008) Activation of transient receptor potential A1 channels by mustard oil, tetrahydrocannabinol and Ca2+ reveals different functional channel states. Neuroscience 154:1467–1476PubMedCrossRefGoogle Scholar
  27. 27.
    Chatzigeorgiou M, Yoo S, Watson JD, Lee WH, Spencer WC, Kindt KS, Hwang SW, Miller DM 3rd, Treinin M, Driscoll M, Schafer WR (2010) Specific roles for DEG/ENaC and TRP channels in touch and thermosensation in C. elegans nociceptors. Nat Neurosci 13:861–868PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Chen J, Kang D, Xu J, Lake M, Hogan JO, Sun C, Walter K, Yao B, Kim D (2013) Species differences and molecular determinant of TRPA1 cold sensitivity. Nat Commun 4:2501PubMedPubMedCentralGoogle Scholar
  29. 29.
    Cho H, Yang YD, Lee J, Lee B, Kim T, Jang Y, Back SK, Na HS, Harfe BD, Wang F, Raouf R, Wood JN, Oh U (2012) The calcium-activated chloride channel anoctamin 1 acts as a heat sensor in nociceptive neurons. Nat Neurosci 15:1015–1021PubMedCrossRefGoogle Scholar
  30. 30.
    Choi JS, Waxman SG (2011) Physiological interactions between Na(v)1.7 and Na(v)1.8 sodium channels: a computer simulation study. J Neurophysiol 106:3173–3184PubMedCrossRefGoogle Scholar
  31. 31.
    Clapham DE, Miller C (2011) A thermodynamic framework for understanding temperature sensing by transient receptor potential (TRP) channels. Proc Natl Acad Sci U S A 108:19492–19497PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Corfas RA, Vosshall LB (2015) The cation channel TRPA1 tunes mosquito thermotaxis to host temperatures. elife 4Google Scholar
  33. 33.
    Cox JJ, Reimann F, Nicholas AK, Thornton G, Roberts E, Springell K, Karbani G, Jafri H, Mannan J, Raashid Y, Al-Gazali L, Hamamy H, Valente EM, Gorman S, Williams R, McHale DP, Wood JN, Gribble FM, Woods CG (2006) An SCN9A channelopathy causes congenital inability to experience pain. Nature 444:894–898PubMedCrossRefGoogle Scholar
  34. 34.
    Cummins TR, Dib-Hajj SD, Waxman SG (2004) Electrophysiological properties of mutant Nav1.7 sodium channels in a painful inherited neuropathy. J Neurosci: Off J Soc Neurosci 24:8232–8236CrossRefGoogle Scholar
  35. 35.
    Davis JB, Gray J, Gunthorpe MJ, Hatcher JP, Davey PT, Overend P, Harries MH, Latcham J, Clapham C, Atkinson K, Hughes SA, Rance K, Grau E, Harper AJ, Pugh PL, Rogers DC, Bingham S, Randall A, Sheardown SA (2000) Vanilloid receptor-1 is essential for inflammatory thermal hyperalgesia. Nature 405:183–187PubMedCrossRefGoogle Scholar
  36. 36.
    del Camino D, Murphy S, Heiry M, Barrett LB, Earley TJ, Cook CA, Petrus MJ, Zhao M, D'Amours M, Deering N, Brenner GJ, Costigan M, Hayward NJ, Chong JA, Fanger CM, Woolf CJ, Patapoutian A, Moran MM (2010) TRPA1 contributes to cold hypersensitivity. J Neurosci: Off J Soc Neurosci 30:15165–15174CrossRefGoogle Scholar
  37. 37.
    Dhaka A, Murray AN, Mathur J, Earley TJ, Petrus MJ, Patapoutian A (2007) TRPM8 is required for cold sensation in mice. Neuron 54:371–378PubMedCrossRefGoogle Scholar
  38. 38.
    Dib-Hajj S, Black JA, Cummins TR, Waxman SG (2002) NaN/Nav1.9: a sodium channel with unique properties. Trends Neurosci 25:253–259PubMedCrossRefGoogle Scholar
  39. 39.
    Dib-Hajj SD, Black JA, Waxman SG (2015) NaV1.9: a sodium channel linked to human pain. Nat Rev Neurosci 16:511–519PubMedCrossRefGoogle Scholar
  40. 40.
    Dib-Hajj SD, Tyrrell L, Black JA, Waxman SG (1998) NaN, a novel voltage-gated Na channel, is expressed preferentially in peripheral sensory neurons and down-regulated after axotomy. Proc Natl Acad Sci U S A 95:8963–8968PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Djouhri L, Newton R, Levinson SR, Berry CM, Carruthers B, Lawson SN (2003) Sensory and electrophysiological properties of guinea-pig sensory neurones expressing Nav 1.7 (PN1) Na+ channel alpha subunit protein. J Physiol 546:565–576PubMedCrossRefGoogle Scholar
  42. 42.
    Enyedi P, Czirjak G (2010) Molecular background of leak K+ currents: two-pore domain potassium channels. Physiol Rev 90:559–605PubMedCrossRefGoogle Scholar
  43. 43.
    Esmann M, Skou JC (1988) Temperature-dependencies of various catalytic activities of membrane-bound Na+/K+-ATPase from ox brain, ox kidney and shark rectal gland and of C12E8-solubilized shark Na+/K+-ATPase. Biochim Biophys Acta 944:344–350PubMedCrossRefGoogle Scholar
  44. 44.
    Faber CG, Lauria G, Merkies IS, Cheng X, Han C, Ahn HS, Persson AK, Hoeijmakers JG, Gerrits MM, Pierro T, Lombardi R, Kapetis D, Dib-Hajj SD, Waxman SG (2012) Gain-of-function Nav1.8 mutations in painful neuropathy. Proc Natl Acad Sci U S A 109:19444–19449PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Fertleman CR, Baker MD, Parker KA, Moffatt S, Elmslie FV, Abrahamsen B, Ostman J, Klugbauer N, Wood JN, Gardiner RM, Rees M (2006) SCN9A mutations in paroxysmal extreme pain disorder: allelic variants underlie distinct channel defects and phenotypes. Neuron 52:767–774PubMedCrossRefGoogle Scholar
  46. 46.
    Galarza-Munoz G, Soto-Morales SI, Holmgren M, Rosenthal JJ (2011) Physiological adaptation of an Antarctic Na+/K+-ATPase to the cold. J Exp Biol 214:2164–2174PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Garrett S, Rosenthal JJ (2012) RNA editing underlies temperature adaptation in K+ channels from polar octopuses. Science (New York, NY) 335:848–851CrossRefGoogle Scholar
  48. 48.
    Gau P, Poon J, Ufret-Vincenty C, Snelson CD, Gordon SE, Raible DW, Dhaka A (2013) The zebrafish ortholog of TRPV1 is required for heat-induced locomotion. J Neurosci: Off J Soc Neurosci 33:5249–5260CrossRefGoogle Scholar
  49. 49.
    Geiser F (2013) Hibernation. Curr Biol: CB 23:R188–R193PubMedCrossRefGoogle Scholar
  50. 50.
    Gracheva EO, Cordero-Morales JF, Gonzalez-Carcacia JA, Ingolia NT, Manno C, Aranguren CI, Weissman JS, Julius D (2011) Ganglion-specific splicing of TRPV1 underlies infrared sensation in vampire bats. Nature 476:88–91PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Gracheva EO, Ingolia NT, Kelly YM, Cordero-Morales JF, Hollopeter G, Chesler AT, Sanchez EE, Perez JC, Weissman JS, Julius D (2010) Molecular basis of infrared detection by snakes. Nature 464:1006–1011PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    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 11:1007–1013PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    Guler AD, Lee H, Iida T, Shimizu I, Tominaga M, Caterina M (2002) Heat-evoked activation of the ion channel, TRPV4. J Neurosci: Off J Soc Neurosci 22:6408–6414CrossRefGoogle Scholar
  54. 54.
    Hoeijmakers JG, Faber CG, Merkies IS, Waxman SG (2015) Painful peripheral neuropathy and sodium channel mutations. Neurosci Lett 596:51–59PubMedCrossRefGoogle Scholar
  55. 55.
    Honore E, Maingret F, Lazdunski M, Patel AJ (2002) An intracellular proton sensor commands lipid- and mechano-gating of the K(+) channel TREK-1. EMBO J 21:2968–2976PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Hudson JW, Deavers DR (1973) Metabolism, pulmocutaneous water loss and respiration of eight species of ground squirrels from different environments. Comp Biochem Physiol A Comp Physiol 45:69–100PubMedCrossRefGoogle Scholar
  57. 57.
    Hwang RY, Stearns NA, Tracey WD (2012) The ankyrin repeat domain of the TRPA protein painless is important for thermal nociception but not mechanical nociception. PLoS One 7:e30090PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Jabba S, Goyal R, Sosa-Pagan JO, Moldenhauer H, Wu J, Kalmeta B, Bandell M, Latorre R, Patapoutian A, Grandl J (2014) Directionality of temperature activation in mouse TRPA1 ion channel can be inverted by single-point mutations in ankyrin repeat six. Neuron 82:1017–1031PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Jordt SE, Bautista DM, Chuang HH, McKemy DD, Zygmunt PM, Hogestatt ED, Meng ID, Julius D (2004) Mustard oils and cannabinoids excite sensory nerve fibres through the TRP channel ANKTM1. Nature 427:260–265PubMedCrossRefGoogle Scholar
  60. 60.
    Jordt SE, Julius D (2002) Molecular basis for species-specific sensitivity to "hot" chili peppers. Cell 108:421–430PubMedCrossRefGoogle Scholar
  61. 61.
    Julius D (2013) TRP channels and pain. Annu Rev Cell Dev Biol 29:355–384PubMedCrossRefGoogle Scholar
  62. 62.
    Kanda H, Gu JG (2017) Effects of cold temperatures on the excitability of rat trigeminal ganglion neurons that are not for cold sensing. J Neurochem 141:532–543PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Kandel ER, Schwartz JH, Jessell TM (2000) Principles of neural science. McGraw-Hill, Health Professions Division, New YorkGoogle Scholar
  64. 64.
    Kang D, Choe C, Kim D (2005) Thermosensitivity of the two-pore domain K+ channels TREK-2 and TRAAK. J Physiol 564:103–116PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Kang K, Panzano VC, Chang EC, Ni L, Dainis AM, Jenkins AM, Regna K, Muskavitch MA, Garrity PA (2011) Modulation of TRPA1 thermal sensitivity enables sensory discrimination in drosophila. Nature 481:76–80PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    Kang K, Pulver SR, Panzano VC, Chang EC, Griffith LC, Theobald DL, Garrity PA (2010) Analysis of drosophila TRPA1 reveals an ancient origin for human chemical nociception. Nature 464:597–600PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Khmyz V, Maximyuk O, Teslenko V, Verkhratsky A, Krishtal O (2008) P2X3 receptor gating near normal body temperature. Pflugers Archiv: Eur J Physiol 456:339–347CrossRefGoogle Scholar
  68. 68.
    Kiss T, Battonyai I, Pirger Z (2014) Down regulation of sodium channels in the central nervous system of hibernating snails. Physiol Behav 131:93–98PubMedCrossRefGoogle Scholar
  69. 69.
    Knecht ZA, Silbering AF, Cruz J, Yang L, Croset V, Benton R, Garrity PA (2017) Ionotropic receptor-dependent moist and dry cells control hygrosensation in drosophila. elife 6Google Scholar
  70. 70.
    Knecht ZA, Silbering AF, Ni L, Klein M, Budelli G, Bell R, Abuin L, Ferrer AJ, Samuel AD, Benton R, Garrity PA (2016) Distinct combinations of variant ionotropic glutamate receptors mediate thermosensation and hygrosensation in drosophila. elife 5Google Scholar
  71. 71.
    Knowlton WM, Bifolck-Fisher A, Bautista DM, McKemy DD (2010) TRPM8, but not TRPA1, is required for neural and behavioral responses to acute noxious cold temperatures and cold-mimetics in vivo. Pain 150:340–350PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Knowlton WM, Palkar R, Lippoldt EK, McCoy DD, Baluch F, Chen J, McKemy DD (2013) A sensory-labeled line for cold: TRPM8-expressing sensory neurons define the cellular basis for cold, cold pain, and cooling-mediated analgesia. J Neurosci: Off J Soc Neurosci 33:2837–2848CrossRefGoogle Scholar
  73. 73.
    Kurganov E, Zhou Y, Saito S, Tominaga M (2014) Heat and AITC activate green anole TRPA1 in a membrane-delimited manner. Pflugers Archiv: Eur J Physiol 466:1873–1884CrossRefGoogle Scholar
  74. 74.
    Kürten L, Schmidt U (1982) Thermoperception in the common vampire bat (Desmodus rotundus). J Comp Physiol 146:223–228CrossRefGoogle Scholar
  75. 75.
    Kwan KY, Allchorne AJ, Vollrath MA, Christensen AP, Zhang DS, Woolf CJ, Corey DP (2006) TRPA1 contributes to cold, mechanical, and chemical nociception but is not essential for hair-cell transduction. Neuron 50:277–289PubMedCrossRefGoogle Scholar
  76. 76.
    Kwon Y, Shim HS, Wang X, Montell C (2008) Control of thermotactic behavior via coupling of a TRP channel to a phospholipase C signaling cascade. Nat Neurosci 11:871–873PubMedCrossRefGoogle Scholar
  77. 77.
    Laing RJ, Dhaka A (2016) ThermoTRPs and Pain. Neuroscientist: Rev J Bring Neurobiol Neurol Psychiatry 22:171–187CrossRefGoogle Scholar
  78. 78.
    Laursen WJ, Anderson EO, Hoffstaetter LJ, Bagriantsev SN, Gracheva EO (2015) Species-specific temperature sensitivity of TRPA1. Temperature (Austin, Tex) 2:214–226CrossRefGoogle Scholar
  79. 79.
    Laursen WJ, Schneider ER, Merriman DK, Bagriantsev SN, Gracheva EO (2016) Low-cost functional plasticity of TRPV1 supports heat tolerance in squirrels and camels. Proc Natl Acad Sci U S A 113:11342–11347PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Lee H, Iida T, Mizuno A, Suzuki M, Caterina MJ (2005) Altered thermal selection behavior in mice lacking transient receptor potential vanilloid 4. J Neurosci: Off J Soc Neurosci 25:1304–1310CrossRefGoogle Scholar
  81. 81.
    Lee Y, Lee Y, Lee J, Bang S, Hyun S, Kang J, Hong ST, Bae E, Kaang BK, Kim J (2005) Pyrexia is a new thermal transient receptor potential channel endowing tolerance to high temperatures in Drosophila Melanogaster. Nat Genet 37:305–310PubMedCrossRefGoogle Scholar
  82. 82.
    Leipold E, Hanson-Kahn A, Frick M, Gong P, Bernstein JA, Voigt M, Katona I, Oliver Goral R, Altmuller J, Nurnberg P, Weis J, Hubner CA, Heinemann SH, Kurth I (2015) Cold-aggravated pain in humans caused by a hyperactive NaV1.9 channel mutant. Nat Commun 6:10049PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Leipold E, Liebmann L, Korenke GC, Heinrich T, Giesselmann S, Baets J, Ebbinghaus M, Goral RO, Stodberg T, Hennings JC, Bergmann M, Altmuller J, Thiele H, Wetzel A, Nurnberg P, Timmerman V, De Jonghe P, Blum R, Schaible HG, Weis J, Heinemann SH, Hubner CA, Kurth I (2013) A de novo gain-of-function mutation in SCN11A causes loss of pain perception. Nat Genet 45:1399–1404PubMedCrossRefGoogle Scholar
  84. 84.
    Lesage F, Terrenoire C, Romey G, Lazdunski M (2000) Human TREK2, a 2P domain mechano-sensitive K+ channel with multiple regulations by polyunsaturated fatty acids, lysophospholipids, and Gs, Gi, and Gq protein-coupled receptors. J Biol Chem 275:28398–28405PubMedCrossRefGoogle Scholar
  85. 85.
    Liu B, Qin F (2016) Use dependence of heat sensitivity of Vanilloid receptor TRPV2. Biophys J 110:1523–1537PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    Liu S, Schulze E, Baumeister R (2012) Temperature- and touch-sensitive neurons couple CNG and TRPV channel activities to control heat avoidance in Caenorhabditis elegans. PLoS One 7:e32360PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Liu Z, Wang W, Zhang TZ, Li GH, He K, Huang JF, Jiang XL, Murphy RW, Shi P (2014) Repeated functional convergent effects of NaV1.7 on acid insensitivity in hibernating mammals. Proc Biol sci 281:20132950PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    Lolicato M, Arrigoni C, Mori T, Sekioka Y, Bryant C, Clark KA, Minor DL Jr (2017) K2P2.1 (TREK-1)-activator complexes reveal a cryptic selectivity filter binding site. Nature 547:364–368PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Lolicato M, Riegelhaupt PM, Arrigoni C, Clark KA, Minor DL Jr (2014) Transmembrane helix straightening and buckling underlies activation of mechanosensitive and thermosensitive K(2P) channels. Neuron 84:1198–1212PubMedPubMedCentralCrossRefGoogle Scholar
  90. 90.
    Lolignier S, Bonnet C, Gaudioso C, Noel J, Ruel J, Amsalem M, Ferrier J, Rodat-Despoix L, Bouvier V, Aissouni Y, Prival L, Chapuy E, Padilla F, Eschalier A, Delmas P, Busserolles J (2015) The Nav1.9 channel is a key determinant of cold pain sensation and cold allodynia. Cell Rep 11:1067–1078PubMedCrossRefGoogle Scholar
  91. 91.
    Maertens C, Cuypers E, Amininasab M, Jalali A, Vatanpour H, Tytgat J (2006) Potent modulation of the voltage-gated sodium channel Nav1.7 by OD1, a toxin from the scorpion Odonthobuthus doriae. Mol Pharmacol 70:405–414PubMedGoogle Scholar
  92. 92.
    Maingret F, Fosset M, Lesage F, Lazdunski M, Honore E (1999) TRAAK is a mammalian neuronal mechano-gated K+ channel. J Biol Chem 274:1381–1387PubMedCrossRefGoogle Scholar
  93. 93.
    Maingret F, Lauritzen I, Patel AJ, Heurteaux C, Reyes R, Lesage F, Lazdunski M, Honore E (2000) TREK-1 is a heat-activated background K(+) channel. EMBO J 19:2483–2491PubMedPubMedCentralCrossRefGoogle Scholar
  94. 94.
    Maingret F, Patel AJ, Lesage F, Lazdunski M, Honore E (1999) Mechano or acid stimulation, two interactive modes of activation of the TREK-1 potassium channel. J Biol Chem 274:26691–26696PubMedCrossRefGoogle Scholar
  95. 95.
    Matos-Cruz V, Schneider ER, Mastrotto M, Merriman DK, Bagriantsev SN, Gracheva EO Molecular prerequisites for diminished cold sensitivity in ground squirrels and hamsters. Cell Rep 21:3329–3337Google Scholar
  96. 96.
    McKemy DD, Neuhausser WM, Julius D (2002) Identification of a cold receptor reveals a general role for TRP channels in thermosensation. Nature 416:52–58PubMedCrossRefGoogle Scholar
  97. 97.
    Memon T, Chase K, Leavitt LS, Olivera BM, Teichert RW (2017) TRPA1 expression levels and excitability brake by KV channels influence cold sensitivity of TRPA1-expressing neurons. Neuroscience 353:76–86PubMedCrossRefGoogle Scholar
  98. 98.
    Merriman DK, Lahvis G, Jooss M, Gesicki JA, Schill K (2012) Current practices in a captive breeding colony of 13-lined ground squirrels (Ictidomys Tridecemlineatus). Lab Animal 41:315–325PubMedCrossRefGoogle Scholar
  99. 99.
    Mishra SK, Tisel SM, Orestes P, Bhangoo SK, Hoon MA (2011) TRPV1-lineage neurons are required for thermal sensation. EMBO J 30:582–593PubMedCrossRefGoogle Scholar
  100. 100.
    Montell C, Birnbaumer L, Flockerzi V, Bindels RJ, Bruford EA, Caterina MJ, Clapham DE, Harteneck C, Heller S, Julius D, Kojima I, Mori Y, Penner R, Prawitt D, Scharenberg AM, Schultz G, Shimizu N, Zhu MX (2002) A unified nomenclature for the superfamily of TRP cation channels. Mol Cell 9:229–231PubMedCrossRefGoogle Scholar
  101. 101.
    Moparthi L, Kichko TI, Eberhardt M, Hogestatt ED, Kjellbom P, Johanson U, Reeh PW, Leffler A, Filipovic MR, Zygmunt PM (2016) Human TRPA1 is a heat sensor displaying intrinsic U-shaped thermosensitivity. Sci Rep 6:28763PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Moparthi L, Survery S, Kreir M, Simonsen C, Kjellbom P, Hogestatt ED, Johanson U, Zygmunt PM (2014) Human TRPA1 is intrinsically cold- and chemosensitive with and without its N-terminal ankyrin repeat domain. Proc Natl Acad Sci U S A 111:16901–16906PubMedPubMedCentralCrossRefGoogle Scholar
  103. 103.
    Moqrich A, Hwang SW, Earley TJ, Petrus MJ, Murray AN, Spencer KS, Andahazy M, Story GM, Patapoutian A (2005) Impaired thermosensation in mice lacking TRPV3, a heat and camphor sensor in the skin. Science (New York, NY) 307:1468–1472CrossRefGoogle Scholar
  104. 104.
    Morenilla-Palao C, Luis E, Fernandez-Pena C, Quintero E, Weaver JL, Bayliss DA, Viana F (2014) Ion channel profile of TRPM8 cold receptors reveals a role of TASK-3 potassium channels in thermosensation. Cell Rep 8:1571–1582PubMedPubMedCentralCrossRefGoogle Scholar
  105. 105.
    Myers BR, Sigal YM, Julius D (2009) Evolution of thermal response properties in a cold-activated TRP channel. PLoS One 4:e5741PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    Nagai K, Saitoh Y, Saito S, Tsutsumi K (2012) Structure and hibernation-associated expression of the transient receptor potential vanilloid 4 channel (TRPV4) mRNA in the Japanese grass lizard (Takydromus tachydromoides). Zool Sci 29:185–190PubMedCrossRefGoogle Scholar
  107. 107.
    Ni L, Bronk P, Chang EC, Lowell AM, Flam JO, Panzano VC, Theobald DL, Griffith LC, Garrity PA (2013) A gustatory receptor paralogue controls rapid warmth avoidance in drosophila. Nature 500:580–584PubMedPubMedCentralCrossRefGoogle Scholar
  108. 108.
    Ni L, Klein M, Svec KV, Budelli G, Chang EC, Ferrer AJ, Benton R, Samuel AD, Garrity PA (2016) The ionotropic receptors IR21a and IR25a mediate cool sensing in drosophila. elife 5Google Scholar
  109. 109.
    Noel J, Zimmermann K, Busserolles J, Deval E, Alloui A, Diochot S, Guy N, Borsotto M, Reeh P, Eschalier A, Lazdunski M (2009) The mechano-activated K+ channels TRAAK and TREK-1 control both warm and cold perception. EMBO J 28:1308–1318PubMedPubMedCentralCrossRefGoogle Scholar
  110. 110.
    Ohkita M, Saito S, Imagawa T, Takahashi K, Tominaga M, Ohta T (2012) Molecular cloning and functional characterization of Xenopus tropicalis frog transient receptor potential vanilloid 1 reveal its functional evolution for heat, acid, and capsaicin sensitivities in terrestrial vertebrates. J Biol Chem 287:2388–2397PubMedCrossRefGoogle Scholar
  111. 111.
    Osteen JD, Herzig V, Gilchrist J, Emrick JJ, Zhang C, Wang X, Castro J, Garcia-Caraballo S, Grundy L, Rychkov GY, Weyer AD, Dekan Z, Undheim EA, Alewood P, Stucky CL, Brierley SM, Basbaum AI, Bosmans F, King GF, Julius D (2016) Selective spider toxins reveal a role for the Nav1.1 channel in mechanical pain. Nature 534:494–499PubMedPubMedCentralCrossRefGoogle Scholar
  112. 112.
    Park TJ, Reznick J, Peterson BL, Blass G, Omerbasic D, Bennett NC, Kuich P, Zasada C, Browe BM, Hamann W, Applegate DT, Radke MH, Kosten T, Lutermann H, Gavaghan V, Eigenbrod O, Begay V, Amoroso VG, Govind V, Minshall RD, Smith ESJ, Larson J, Gotthardt M, Kempa S, Lewin GR (2017) Fructose-driven Glycolysis supports anoxia resistance in the naked mole-rat. Science (New York, NY) 356:307–311CrossRefGoogle Scholar
  113. 113.
    Passmore GM, Selyanko AA, Mistry M, Al-Qatari M, Marsh SJ, Matthews EA, Dickenson AH, Brown TA, Burbidge SA, Main M, Brown DA (2003) KCNQ/M currents in sensory neurons: significance for pain therapy. J Neurosci: Off J Soc Neurosci 23:7227–7236CrossRefGoogle Scholar
  114. 114.
    Patel AJ, Honore E, Maingret F, Lesage F, Fink M, Duprat F, Lazdunski M (1998) A mammalian two pore domain mechano-gated S-like K+ channel. EMBO J 17:4283–4290PubMedPubMedCentralCrossRefGoogle Scholar
  115. 115.
    Peier AM, Moqrich A, Hergarden AC, Reeve AJ, Andersson DA, Story GM, Earley TJ, Dragoni I, McIntyre P, Bevan S, Patapoutian A (2002) A TRP channel that senses cold stimuli and menthol. Cell 108:705–715PubMedCrossRefGoogle Scholar
  116. 116.
    Pereira V, Busserolles J, Christin M, Devilliers M, Poupon L, Legha W, Alloui A, Aissouni Y, Bourinet E, Lesage F, Eschalier A, Lazdunski M, Noel J (2014) Role of the TREK2 potassium channel in cold and warm thermosensation and in pain perception. Pain 155:2534–2544PubMedCrossRefGoogle Scholar
  117. 117.
    Phuket TR, Covarrubias M (2009) Kv4 channels underlie the subthreshold-operating A-type K-current in nociceptive dorsal root ganglion neurons. Front Mol Neurosci 2:3PubMedPubMedCentralCrossRefGoogle Scholar
  118. 118.
    Pierau FK, Torrey P, Carpenter DO (1974) Mammalian cold receptor afferents: role of an electrogenic sodium pump in sensory transduction. Brain Res 73:156–160PubMedCrossRefGoogle Scholar
  119. 119.
    Pogorzala LA, Mishra SK, Hoon MA (2013) The cellular code for mammalian thermosensation. J Neurosci: Off J Soc Neurosci 33:5533–5541CrossRefGoogle Scholar
  120. 120.
    Rasband MN, Park EW, Vanderah TW, Lai J, Porreca F, Trimmer JS (2001) Distinct potassium channels on pain-sensing neurons. Proc Natl Acad Sci U S A 98:13373–13378PubMedPubMedCentralCrossRefGoogle Scholar
  121. 121.
    Rowe AH, Xiao Y, Rowe MP, Cummins TR, Zakon HH (2013) Voltage-gated sodium channel in grasshopper mice defends against bark scorpion toxin. Science (New York, NY) 342:441–446CrossRefGoogle Scholar
  122. 122.
    Rytz R, Croset V, Benton R (2013) Ionotropic receptors (IRs): chemosensory ionotropic glutamate receptors in drosophila and beyond. Insect Biochem Mol Biol 43:888–897PubMedCrossRefGoogle Scholar
  123. 123.
    Saito S, Banzawa N, Fukuta N, Saito CT, Takahashi K, Imagawa T, Ohta T, Tominaga M (2014) Heat and noxious chemical sensor, chicken TRPA1, as a target of bird repellents and identification of its structural determinants by multispecies functional comparison. Mol Biol Evol 31:708–722PubMedCrossRefGoogle Scholar
  124. 124.
    Saito S, Nakatsuka K, Takahashi K, Fukuta N, Imagawa T, Ohta T, Tominaga M (2012) Analysis of transient receptor potential ankyrin 1 (TRPA1) in frogs and lizards illuminates both nociceptive heat and chemical sensitivities and coexpression with TRP vanilloid 1 (TRPV1) in ancestral vertebrates. J Biol Chem 287:30743–30754PubMedPubMedCentralCrossRefGoogle Scholar
  125. 125.
    Saito S, Ohkita M, Saito CT, Takahashi K, Tominaga M, Ohta T (2016) Evolution of heat sensors drove shifts in Thermosensation between Xenopus species adapted to different thermal niches. J Biol Chem 291:11446–11459PubMedPubMedCentralCrossRefGoogle Scholar
  126. 126.
    Sandoz G, Douguet D, Chatelain F, Lazdunski M, Lesage F (2009) Extracellular acidification exerts opposite actions on TREK1 and TREK2 potassium channels via a single conserved histidine residue. Proc Natl Acad Sci U S A 106:14628–14633PubMedPubMedCentralCrossRefGoogle Scholar
  127. 127.
    Sangameswaran L, Fish LM, Koch BD, Rabert DK, Delgado SG, Ilnicka M, Jakeman LB, Novakovic S, Wong K, Sze P, Tzoumaka E, Stewart GR, Herman RC, Chan H, Eglen RM, Hunter JC (1997) A novel tetrodotoxin-sensitive, voltage-gated sodium channel expressed in rat and human dorsal root ganglia. J Biol Chem 272:14805–14809PubMedCrossRefGoogle Scholar
  128. 128.
    Sarria I, Ling J, Gu JG (2012) Thermal sensitivity of voltage-gated Na+ channels and A-type K+ channels contributes to somatosensory neuron excitability at cooling temperatures. J Neurochem 122:1145–1154PubMedPubMedCentralCrossRefGoogle Scholar
  129. 129.
    Sarria I, Ling J, Xu GY, Gu JG (2012) Sensory discrimination between innocuous and noxious cold by TRPM8-expressing DRG neurons of rats. Mol Pain 8:79PubMedPubMedCentralCrossRefGoogle Scholar
  130. 130.
    Schneider ER, Anderson EO, Gracheva EO, Bagriantsev SN (2014) Temperature sensitivity of two-pore (K2P) potassium channels. Curr Top Membr 74:113–133PubMedPubMedCentralCrossRefGoogle Scholar
  131. 131.
    Shen WL, Kwon Y, Adegbola AA, Luo J, Chess A, Montell C (2011) Function of rhodopsin in temperature discrimination in drosophila. Science (New York, NY) 331:1333–1336CrossRefGoogle Scholar
  132. 132.
    Shimizu I, Iida T, Guan Y, Zhao C, Raja SN, Jarvis MF, Cockayne DA, Caterina MJ (2005) Enhanced thermal avoidance in mice lacking the ATP receptor P2X3. Pain 116:96–108PubMedCrossRefGoogle Scholar
  133. 133.
    Smith ES, Omerbasic D, Lechner SG, Anirudhan G, Lapatsina L, Lewin GR (2011) The molecular basis of acid insensitivity in the African naked mole-rat. Science (New York, NY) 334:1557–1560CrossRefGoogle Scholar
  134. 134.
    Smith GD, Gunthorpe MJ, Kelsell RE, Hayes PD, Reilly P, Facer P, Wright JE, Jerman JC, Walhin JP, Ooi L, Egerton J, Charles KJ, Smart D, Randall AD, Anand P, Davis JB (2002) TRPV3 is a temperature-sensitive vanilloid receptor-like protein. Nature 418:186–190PubMedCrossRefGoogle Scholar
  135. 135.
    Sokabe T, Chen HC, Luo J, Montell C (2016) A switch in thermal preference in drosophila larvae depends on multiple Rhodopsins. Cell Rep 17:336–344PubMedPubMedCentralCrossRefGoogle Scholar
  136. 136.
    Sokabe T, Tsujiuchi S, Kadowaki T, Tominaga M (2008) Drosophila painless is a Ca2+-requiring channel activated by noxious heat. J Neurosci: Off J Soc Neurosci 28:9929–9938CrossRefGoogle Scholar
  137. 137.
    Souslova V, Cesare P, Ding Y, Akopian AN, Stanfa L, Suzuki R, Carpenter K, Dickenson A, Boyce S, Hill R, Nebenuis-Oosthuizen D, Smith AJ, Kidd EJ, Wood JN (2000) Warm-coding deficits and aberrant inflammatory pain in mice lacking P2X3 receptors. Nature 407:1015–1017PubMedCrossRefGoogle Scholar
  138. 138.
    Story GM, Peier AM, Reeve AJ, Eid SR, Mosbacher J, Hricik TR, Earley TJ, Hergarden AC, Andersson DA, Hwang SW, McIntyre P, Jegla T, Bevan S, Patapoutian A (2003) ANKTM1, a TRP-like channel expressed in nociceptive neurons, is activated by cold temperatures. Cell 112:819–829PubMedCrossRefGoogle Scholar
  139. 139.
    Straub I, Krugel U, Mohr F, Teichert J, Rizun O, Konrad M, Oberwinkler J, Schaefer M (2013) Flavanones that selectively inhibit TRPM3 attenuate thermal nociception in vivo. Mol Pharmacol 84:736–750PubMedCrossRefGoogle Scholar
  140. 140.
    Talavera K, Yasumatsu K, Voets T, Droogmans G, Shigemura N, Ninomiya Y, Margolskee RF, Nilius B (2005) Heat activation of TRPM5 underlies thermal sensitivity of sweet taste. Nature 438:1022–1025PubMedCrossRefGoogle Scholar
  141. 141.
    Tan CH, McNaughton PA (2016) The TRPM2 ion channel is required for sensitivity to warmth. Nature 536:460–463PubMedPubMedCentralCrossRefGoogle Scholar
  142. 142.
    Toledo-Aral JJ, Moss BL, He ZJ, Koszowski AG, Whisenand T, Levinson SR, Wolf JJ, Silos-Santiago I, Halegoua S, Mandel G (1997) Identification of PN1, a predominant voltage-dependent sodium channel expressed principally in peripheral neurons. Proc Natl Acad Sci U S A 94:1527–1532PubMedPubMedCentralCrossRefGoogle Scholar
  143. 143.
    Tominaga M, Caterina MJ, Malmberg AB, Rosen TA, Gilbert H, Skinner K, Raumann BE, Basbaum AI, Julius D (1998) The cloned capsaicin receptor integrates multiple pain-producing stimuli. Neuron 21:531–543PubMedCrossRefGoogle Scholar
  144. 144.
    Tracey WD Jr, Wilson RI, Laurent G, Benzer S (2003) Painless, a drosophila gene essential for nociception. Cell 113:261–273PubMedCrossRefGoogle Scholar
  145. 145.
    Viana F, de la Pena E, Belmonte C (2002) Specificity of cold thermotransduction is determined by differential ionic channel expression. Nat Neurosci 5:254–260PubMedCrossRefGoogle Scholar
  146. 146.
    Voets T (2012) Quantifying and modeling the temperature-dependent gating of TRP channels. Rev Physiol Biochem Pharmacol 162:91–119PubMedGoogle Scholar
  147. 147.
    Vriens J, Owsianik G, Hofmann T, Philipp SE, Stab J, Chen X, Benoit M, Xue F, Janssens A, Kerselaers S, Oberwinkler J, Vennekens R, Gudermann T, Nilius B, Voets T (2011) TRPM3 is a nociceptor channel involved in the detection of noxious heat. Neuron 70:482–494PubMedCrossRefGoogle Scholar
  148. 148.
    Vydyanathan A, Wu ZZ, Chen SR, Pan HL (2005) A-type voltage-gated K+ currents influence firing properties of isolectin B4-positive but not isolectin B4-negative primary sensory neurons. J Neurophysiol 93:3401–3409PubMedCrossRefGoogle Scholar
  149. 149.
    Wang G, Qiu YT, Lu T, Kwon HW, Pitts RJ, van Loon JJ, Takken W, Zwiebel LJ (2009) Anopheles gambiae TRPA1 is a heat-activated channel expressed in thermosensitive sensilla of female antennae. Eur J Neurosci 30:967–974PubMedPubMedCentralCrossRefGoogle Scholar
  150. 150.
    Wang HS, Pan Z, Shi W, Brown BS, Wymore RS, Cohen IS, Dixon JE, McKinnon D (1998) KCNQ2 and KCNQ3 potassium channel subunits: molecular correlates of the M-channel. Science (New York, NY) 282:1890–1893CrossRefGoogle Scholar
  151. 151.
    Watanabe H, Vriens J, Suh SH, Benham CD, Droogmans G, Nilius B (2002) Heat-evoked activation of TRPV4 channels in a HEK293 cell expression system and in native mouse aorta endothelial cells. J Biol Chem 277:47044–47051PubMedCrossRefGoogle Scholar
  152. 152.
    Waxman SG, Zamponi GW (2014) Regulating excitability of peripheral afferents: emerging ion channel targets. Nat Neurosci 17:153–163PubMedCrossRefGoogle Scholar
  153. 153.
    Xiao B, Coste B, Mathur J, Patapoutian A (2011) Temperature-dependent STIM1 activation induces Ca(2)+ influx and modulates gene expression. Nat Chem Biol 7:351–358PubMedPubMedCentralCrossRefGoogle Scholar
  154. 154.
    Xiao R, Zhang B, Dong Y, Gong J, Xu T, Liu J, Xu XZ (2013) A genetic program promotes C. elegans longevity at cold temperatures via a thermosensitive TRP channel. Cell 152:806–817PubMedPubMedCentralCrossRefGoogle Scholar
  155. 155.
    Xu H, Ramsey IS, Kotecha SA, Moran MM, Chong JA, Lawson D, Ge P, Lilly J, Silos-Santiago I, Xie Y, DiStefano PS, Curtis R, Clapham DE (2002) TRPV3 is a calcium-permeable temperature-sensitive cation channel. Nature 418:181–186PubMedCrossRefGoogle Scholar
  156. 156.
    Yamamoto Y, Hatakeyama T, Taniguchi K (2009) Immunohistochemical colocalization of TREK-1, TREK-2 and TRAAK with TRP channels in the trigeminal ganglion cells. Neurosci Lett 454:129–133PubMedCrossRefGoogle Scholar
  157. 157.
    Zakon HH (2012) Adaptive evolution of voltage-gated sodium channels: the first 800 million years. Proc Natl Acad Sci U S A 109(Suppl 1):10619–10625PubMedPubMedCentralCrossRefGoogle Scholar
  158. 158.
    Zhong L, Bellemer A, Yan H, Ken H, Jessica R, Hwang RY, Pitt GS, Tracey WD (2012) Thermosensory and nonthermosensory isoforms of Drosophila melanogaster TRPA1 reveal heat-sensor domains of a thermoTRP channel. Cell Rep 1:43–55PubMedPubMedCentralCrossRefGoogle Scholar
  159. 159.
    Zimmermann K, Leffler A, Babes A, Cendan CM, Carr RW, Kobayashi J, Nau C, Wood JN, Reeh PW (2007) Sensory neuron sodium channel Nav1.8 is essential for pain at low temperatures. Nature 447:855–858PubMedCrossRefGoogle Scholar
  160. 160.
    Zimmermann K, Lennerz JK, Hein A, Link AS, Kaczmarek JS, Delling M, Uysal S, Pfeifer JD, Riccio A, Clapham DE (2011) Transient receptor potential cation channel, subfamily C, member 5 (TRPC5) is a cold-transducer in the peripheral nervous system. Proc Natl Acad Sci U S A 108:18114–18119PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Lydia J. Hoffstaetter
    • 1
    • 2
    • 3
  • Sviatoslav N. Bagriantsev
    • 1
  • Elena O. Gracheva
    • 1
    • 2
    • 3
  1. 1.Department of Cellular and Molecular PhysiologyYale University School of MedicineNew HavenUSA
  2. 2.Department of NeuroscienceYale University School of MedicineNew HavenUSA
  3. 3.Program in Cellular Neuroscience, Neurodegeneration and RepairYale University School of MedicineNew HavenUSA

Personalised recommendations