Abstract
ThermoTRPs are unique channels that mediate Na+ and Ca2+ currents in response to changes in ambient temperature. In combination with their activation by other physical and chemical stimuli, they are considered key integrators of environmental cues into neuronal excitability. Furthermore, roles of thermoTRPs in non-neuronal tissues are currently emerging such as insulin secretion in pancreatic β-cells, and links to cancer. Calcium permeability through thermoTRPs appears a central hallmark for their physiological and pathological activities. Moreover, it is currently being proposed that beyond working as a second messenger, Ca2+ can function locally by acting on protein complexes near the membrane. Interestingly, thermoTRPs can enhance and expand the inherent plasticity of signalplexes by conferring them temperature, pH and lipid regulation through Ca2+ signalling. Thus, unveiling the local role of Ca2+ fluxes induced by thermoTRPs on the dynamics of membrane-attached signalling complexes as well as their significance in cellular processes, are central issues that will expand the opportunities for therapeutic intervention in disorders involving dysfunction of thermoTRP channels.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Nilius B, Flockerzi V (2014) Mammalian transient receptor potential (TRP) cation channels. Handbook of experimental pharmacology, vol 222. Springer, Berlin
Nilius B, Owsianik G, Voets T, Peters JA (2007) Transient receptor potential cation channels in disease. Physiol Rev 87(1):165–217
Venkatachalam K, Montell C (2007) TRP channels. Annu Rev Biochem 76:387–417
Baez D, Raddatz N, Ferreira G, Gonzalez C, Latorre R (2014) Gating of thermally activated channels. Curr Top Membr 74:51–87. doi:10.1016/B978-0-12-800181-3.00003-8
Brederson JD, Kym PR, Szallasi A (2013) Targeting TRP channels for pain relief. Eur J Pharmacol 716(1–3):61–76
Latorre R, Brauchi S, Orta G, Zaelzer C, Vargas G (2007) ThermoTRP channels as modular proteins with allosteric gating. Cell Calcium 42(4–5):427–438
Schepers RJ, Ringkamp M (2010) Thermoreceptors and thermosensitive afferents. Neurosci Biobehav Rev 34(2):177–184
Fernandez-Carvajal A, Fernandez-Ballester G, Devesa I, Gonzalez-Ros JM, Ferrer-Montiel A (2011) New strategies to develop novel pain therapies: addressing thermoreceptors from different points of view. Pharm (Basel) 5(1):16–48
Ferrer-Montiel A, Fernandez-Carvajal A, Planells-Cases R, Fernandez-Ballester G, Gonzalez-Ros JM, Messeguer A, Gonzalez-Muniz R (2012) Advances in modulating thermosensory TRP channels. Expert Opin Ther Pathol 22(9):999–1017
Cvetkov TL, Huynh KW, Cohen MR, Moiseenkova-Bell VY (2011) Molecular architecture and subunit organization of TRPA1 ion channel revealed by electron microscopy. J Biol Chem 286(44):38168–38176
Huynh KW, Cohen MR, Chakrapani S, Holdaway HA, Stewart PL, Moiseenkova-Bell VY (2014) Structural insight into the assembly of TRPV channels. Structure 22(2):260–268
Liao M, Cao E, Julius D, Cheng Y (2013) Structure of the TRPV1 ion channel determined by electron cryo-microscopy. Nature 504(7478):107–112
Moiseenkova-Bell VY, Stanciu LA, Serysheva II, Tobe BJ, Wensel TG (2008) Structure of TRPV1 channel revealed by electron cryomicroscopy. Proc Natl Acad Sci U S A 105(21):7451–7455
Cao E, Liao M, Cheng Y, Julius D (2013) TRPV1 structures in distinct conformations reveal activation mechanisms. Nature 504:113–118
Phelps CB, Huang RJ, Lishko PV, Wang RR, Gaudet R (2008) Structural analyses of the ankyrin repeat domain of TRPV6 and related TRPV ion channels. Biochemistry 47(8):2476–2484
Garcia-Sanz N, Fernandez-Carvajal A, Morenilla-Palao C, Planells-Cases R, Fajardo-Sanchez E, Fernandez-Ballester G, Ferrer-Montiel A (2004) Identification of a tetramerization domain in the C terminus of the vanilloid receptor. J Neurosci 24(23):5307–5314
Garcia-Sanz N, Valente P, Gomis A, Fernandez-Carvajal A, Fernandez-Ballester G, Viana F, Belmonte C, Ferrer-Montiel A (2007) A role of the transient receptor potential domain of vanilloid receptor I in channel gating. J Neurosci 27(43):11641–11650
Valente P, Garcia-Sanz N, Gomis A, Fernandez-Carvajal A, Fernandez-Ballester G, Viana F, Belmonte C, Ferrer-Montiel A (2008) Identification of molecular determinants of channel gating in the transient receptor potential box of vanilloid receptor I. FASEB J 22:3298–3309
Gregorio-Teruel L, Valente P, González-Ros JM, Fernández-Ballester G, Ferrer-Montiel A (2014) Mutation of I696 and W697 in the TRP box of vanilloid receptor subtype I modulates allosteric channel activation. J Gen Physiol 143:361–375
Taberner FJ, Lopez-Cordoba A, Fernandez-Ballester G, Korchev Y, Ferrer-Montiel A (2014) The region adjacent to the C-end of the inner gate in transient receptor potential melastatin 8 (TRPM8) channels plays a central role in allosteric channel activation. J Biol Chem 289(41):28579–28594
Nilius B, Vennekens R, Prenen J, Hoenderop JGJ, Droogmans G, Bindels RJM (2001) The single pore residue Asp542 determines Ca2+ permeation and Mg2+ block of the epithelial Ca2+ channel. J Biol Chem 276:1020–1025
Talavera K, Staes M, Janssens A, Klugbauer N, Droogmans G, Hofmann F, Nilius B (2001) Aspartate residues of the Glu-Glu-Asp-Asp (EEDD) pore locus control selectivity and permeation of the T-type Ca2+channel α1G. J Biol Chem 276:45628–45635
Tang L, Gamal El-Din TM, Payandeh J, Martinez GQ, Heard TM, Scheuer T, Zheng N, Catterall WA (2013) Structural basis for Ca2+ selectivity of a voltage-gated calcium channel. Nat Adv Online Publ 505(7481):56
Yang J, Elllnor PT, Sather WA, Zhang J-F, Tsien RW (1993) Molecular determinants of Ca2+ selectivity and ion permeation in L-type Ca2+ channels. Nature 366:158–161
Nilius B, Prenen J, Janssens A, Owsianik G, Wang C, Zhu MX, Voets T (2005) The selectivity filter of the cation channel TRPM4. J Biol Chem 280:22899–22906
Mederos y Schnitzler M, Wäring J, Gudermann T, Chubanov V (2008) Evolutionary determinants of divergent calcium selectivity of TRPM channels. FASEB J 22:1540–1551
Garcı́a-Martı́nez C, Morenilla-Palao C, Planells-Cases R, Merino JM, Ferrer-Montiel A (2000) Identification of an aspartic residue in the P-loop of the vanilloid receptor that modulates pore properties. J Biol Chem 275:32552–32558
Voets T, Prenen J, Vriens J, Watanabe H, Janssens A, Wissenbach U, Bödding M, Droogmans G, Nilius B (2002) Molecular determinants of permeation through the cation channel TRPV4. J Biol Chem 277:33704–33710
Xia R, Mei Z-Z, Mao H-J, Yang W, Dong L, Bradley H, Beech DJ, Jiang L-H (2008) Identification of pore residues engaged in determining divalent cationic permeation in transient receptor potential melastatin subtype channel 2. J Biol Chem 283:27426–27432
Darré L, Furini S, Domene C (2015) Permeation and dynamics of an open-activated TRPV1 channel. J Mol Biol 427:537–549
Chung M-K, Güler AD, Caterina MJ (2008) TRPV1 shows dynamic ionic selectivity during agonist stimulation. Nat Neurosci 11:555–564
Banke TG, Chaplan SR, Wickenden AD (2010) Dynamic changes in the TRPA1 selectivity filter lead to progressive but reversible pore dilation. Am J Physiol Cell Physiol 298:C1457–C1468
Karashima Y, Prenen J, Talavera K, Janssens A, Voets T, Nilius B (2010) Agonist-induced changes in Ca2+ permeation through the nociceptor cation channel TRPA1. Biophys J 98:773–783
Chen J, Kim D, Bianchi BR, Cavanaugh EJ, Faltynek CR, Kym PR, Reilly RM (2009) Pore dilation occurs in TRPA1 but not in TRPM8 channels. Mol Pain 5:3
Veldhuis NA, Lew MJ, Abogadie FC, Poole DP, Jennings EA, Ivanusic JJ, Eilers H, Bunnett NW, McIntyre P (2012) N-glycosylation determines ionic permeability and desensitization of the TRPV1 capsaicin receptor. J Biol Chem 287:21765–21772
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(44):18114–18119
Schilling WP, Goel M (2004) Mammalian TRPC channel subunit assembly. Novartis Found Symp 258:18–30; discussion 30–43, 98–102, 263–266
Strübing C, Krapivinsky G, Krapivinsky L, Clapham DE (2001) TRPC1 and TRPC5 form a novel cation channel in mammalian brain. Neuron 29:645–655
Strübing C, Krapivinsky G, Krapivinsky L, Clapham DE (2003) Formation of novel TRPC channels by complex subunit interactions in embryonic brain. J Biol Chem 278:39014–39019
Cheng H, Beck A, Launay P, Gross SA, Stokes AJ, Kinet JP, Fleig A, Penner R (2007) TRPM4 controls insulin secretion in pancreatic beta-cells. Cell Calcium 41(1):51–61
Hellwig N, Albrecht N, Harteneck C, Schultz G, Schaefer M (2005) Homo- and heteromeric assembly of TRPV channel subunits. J Cell Sci 118:917–928
Fischer MJM, Balasuriya D, Jeggle P, Goetze TA, McNaughton PA, Reeh PW, Edwardson JM (2014) Direct evidence for functional TRPV1/TRPA1 heteromers. Pflugers Arch – Eur J Physiol 466:2229–2241
Köttgen M, Buchholz B, Garcia-Gonzalez MA, Kotsis F, Fu X, Doerken M, Boehlke C, Steffl D, Tauber R, Wegierski T, Nitschke R, Suzuki M, Kramer-Zucker A, Germino GG, Watnick T, Prenen J, Nilius B, Kuehn EW, Walz G (2008) TRPP2 and TRPV4 form a polymodal sensory channel complex. J Cell Biol 182:437–447
Ma X, Nilius B, Wong JW-Y, Huang Y, Yao X (2011) Electrophysiological properties of heteromeric TRPV4–C1 channels. Biochim Biophys Acta Biomembr 1808:2789–2797
Ma X, Cheng K-T, Wong C-O, O’Neil RG, Birnbaumer L, Ambudkar IS, Yao X (2011) Heteromeric TRPV4-C1 channels contribute to store-operated Ca2+ entry in vascular endothelial cells. Cell Calcium 50:502–509
Stewart AP, Smith GD, Sandford RN, Edwardson JM (2010) Atomic force microscopy reveals the alternating subunit arrangement of the TRPP2-TRPV4 heterotetramer. Biophys J 99:790–797
Launay P, Fleig A, Perraud A-L, Scharenberg AM, Penner R, Kinet J-P (2002) TRPM4 is a Ca2+-activated nonselective cation channel mediating cell membrane depolarization. Cell 109:397–407
Hofmann T, Chubanov V, Gudermann T, Montell C (2003) TRPM5 is a voltage-modulated and Ca2+-activated monovalent selective cation channel. Curr Biol 13:1153–1158
Nilius B, Prenen J, Tang J, Wang C, Owsianik G, Janssens A, Voets T, Zhu MX (2005) Regulation of the Ca2+ sensitivity of the nonselective cation channel TRPM4. J Biol Chem 280:6423–6433
Yamaguchi S, Tanimoto A, K-i O, Hibino H, Ito S (2014) Negatively charged amino acids near and in transient receptor potential (TRP) domain of TRPM4 channel are one determinant of its Ca2+ sensitivity. J Biol Chem 289:35265–35282
Gross SA, Guzmán GA, Wissenbach U, Philipp SE, Zhu MX, Bruns D, Cavalié A (2009) TRPC5 is a Ca2+-activated channel functionally coupled to Ca2+-selective ion channels. J Biol Chem 284:34423–34432
Zholos AV (2014) TRPC5. In: Nilius B, Flockerzi V (eds) Mammalian transient receptor potential (TRP) cation channels. Handbook of experimental pharmacology. Springer, Berlin, pp 129–156
Mahieu F, Janssens A, Gees M, Talavera K, Nilius B, Voets T (2010) Modulation of the cold-activated cation channel TRPM8 by surface charge screening. J Physiol 588(Pt 2):315–324
Doerner JF, Hatt H, Ramsey IS (2011) Voltage- and temperature-dependent activation of TRPV3 channels is potentiated by receptor-mediated PI(4,5)P2 hydrolysis. J Gen Physiol 137:271–288
Zurborg S, Yurgionas B, Jira JA, Caspani O, Heppenstall PA (2007) Direct activation of the ion channel TRPA1 by Ca2+. Nat Neurosci 10:277–279
Nilius B, Voets T, Peters J (2005) TRP channels in disease. Sci STKE 2005(295):re8
O’Neil RG, Brown RC (2003) The vanilloid receptor family of calcium-permeable channels: molecular integrators of microenvironmental stimuli. News Physiol Sci 18:226–231
Benham CD, Davis JB, Randall AD (2002) Vanilloid and TRP channels: a family of lipid-gated cation channels. Neuropharmacology 42(7):873–888
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(6653):816–824
McNamara FN, Randall A, Gunthorpe MJ (2005) Effects of piperine, the pungent component of black pepper, at the human vanilloid receptor (TRPV1). Br J Pharmacol 144:781–790
Akopian AN, Ruparel NB, Jeske NA, Hargreaves KM (2007) Transient receptor potential TRPA1 channel desensitization in sensory neurons is agonist dependent and regulated by TRPV1-directed internalization. J Physiol 583:175–193
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(3):531–543
Bevan S, Hothi S, Hughes G, James IF, Rang HP, Shah K, Walpole CS, Yeats JC (1992) Capsazepine: a competitive antagonist of the sensory neurone excitant capsaicin. Br J Pharmacol 107:544–552
Valente P, Fernández-Carvajal A, Camprubí-Robles M, Gomis A, Quirce S, Viana F, Fernández-Ballester G, González-Ros JM, Belmonte C, Planells-Cases R, Ferrer-Montiel A (2011) Membrane-tethered peptides patterned after the TRP domain (TRPducins) selectively inhibit TRPV1 channel activity. FASEB J 25:1628–1640
Valenzano KJ, Grant ER, Wu G, Hachicha M, Schmid L, Tafesse L, Sun Q, Rotshteyn Y, Francis J, Limberis J, Malik S, Whittemore ER, Hodges D (2003) N-(4-tertiarybutylphenyl)-4-(3-chloropyridin-2-yl)tetrahydropyrazine -1(2H)-carbox-amide (BCTC), a novel, orally effective vanilloid receptor 1 antagonist with analgesic properties: I. In vitro characterization and pharmacokinetic properties. J Pharmacol Exp Ther 306:377–386
Gavva NR, Klionsky L, Qu Y, Shi L, Tamir R, Edenson S, Zhang TJ, Viswanadhan VN, Toth A, Pearce LV, Vanderah TW, Porreca F, Blumberg PM, Lile J, Sun Y, Wild K, Louis J-C, Treanor JJS (2004) Molecular determinants of vanilloid sensitivity in TRPV1. J Biol Chem 279:20283–20295
Jordt S-E, Julius D (2002) Molecular basis for species-specific sensitivity to “hot” chili peppers. Cell 108:421–430
Yao J, Liu B, Qin F (2011) Modular thermal sensors in temperature-gated transient receptor potential (TRP) channels. Proc Natl Acad Sci 108:11109–11114
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(3):362–373
Kim SE, Patapoutian A, Grandl J (2013) Single residues in the outer pore of TRPV1 and TRPV3 have temperature-dependent conformations. PLoS One 8(3):e59593
Brauchi S, Orta G, Salazar M, Rosenmann E, Latorre R (2006) A hot-sensing cold receptor: C-terminal domain determines thermosensation in transient receptor potential channels. J Neurosci 26:4835–4840
Docherty RJ, Yeats JC, Bevan S, Boddeke HW (1996) Inhibition of calcineurin inhibits the desensitization of capsaicin-evoked currents in cultured dorsal root ganglion neurones from adult rats. Pflugers Arch – Eur J Physiol 431(6):828–837
Koplas PA, Rosenberg RL, Oxford GS (1997) The role of calcium in the desensitization of capsaicin responses in rat dorsal root ganglion neurons. J Neurosci 17(10):3525–3537
Lukacs V, Rives J-M, Sun X, Zakharian E, Rohacs T (2013) Promiscuous activation of transient receptor potential vanilloid 1 (TRPV1) channels by negatively charged intracellular lipids. The key role of endogenous phosphoinositides in maintaining channel activity. J Biol Chem 288:35003–35013
Devesa I, Planells-Cases R, Fernandez-Ballester G, Gonzalez-Ros JM, Ferrer-Montiel A, Fernandez-Carvajal A (2011) Role of the transient receptor potential vanilloid 1 in inflammation and sepsis. J Inflamm Res 4:67–81
Planells-Cases R, Valente P, Ferrer-Montiel A, Qin F, Szallasi A (2011) Complex regulation of TRPV1 and related thermo-TRPs: implications for therapeutic intervention. Adv Exp Med Biol 704:491–515
Camprubi-Robles M, Planells-Cases R, Ferrer-Montiel A (2009) Differential contribution of SNARE-dependent exocytosis to inflammatory potentiation of TRPV1 in nociceptors. FASEB J 23(11):3722–3733
Morenilla-Palao C, Planells-Cases R, Garcia-Sanz N, Ferrer-Montiel A (2004) Regulated exocytosis contributes to protein kinase C potentiation of vanilloid receptor activity. J Biol Chem 279(24):25665–25672
Price TJ, Flores CM (2007) Critical evaluation of the colocalization between calcitonin gene-related peptide, substance P, transient receptor potential vanilloid subfamily type 1 immunoreactivities, and isolectin B4 binding in primary afferent neurons of the rat and mouse. J Pain 8(3):263–272
Devesa I, Ferrandiz-Huertas C, Mathivanan S, Wolf C, Lujan R, Changeux JP, Ferrer-Montiel A (2014) alphaCGRP is essential for algesic exocytotic mobilization of TRPV1 channels in peptidergic nociceptors. Proc Natl Acad Sci U S A 111(51):18345–18350
Barton NJ, McQueen DS, Thomson D, Gauldie SD, Wilson AW, Salter DM, Chessell IP (2006) Attenuation of experimental arthritis in TRPV1R knockout mice. Exp Mol Pathol 81(2):166–170
Keeble J, Russell F, Curtis B, Starr A, Pinter E, Brain SD (2005) Involvement of transient receptor potential vanilloid 1 in the vascular and hyperalgesic components of joint inflammation. Arthritis Rheum 52(10):3248–3256
Engler A, Aeschlimann A, Simmen BR, Michel BA, Gay RE, Gay S, Sprott H (2007) Expression of transient receptor potential vanilloid 1 (TRPV1) in synovial fibroblasts from patients with osteoarthritis and rheumatoid arthritis. Biochem Biophys Res Commun 359(4):884–888
Menendez L, Juarez L, Garcia E, Garcia-Suarez O, Hidalgo A, Baamonde A (2006) Analgesic effects of capsazepine and resiniferatoxin on bone cancer pain in mice. Neurosci Lett 393(1):70–73
Hong S, Wiley JW (2005) Early painful diabetic neuropathy is associated with differential changes in the expression and function of vanilloid receptor 1. J Biol Chem 280(1):618–627
Jhaveri MD, Elmes SJ, Kendall DA, Chapman V (2005) Inhibition of peripheral vanilloid TRPV1 receptors reduces noxious heat-evoked responses of dorsal horn neurons in naive, carrageenan-inflamed and neuropathic rats. Eur J Neurosci 22(2):361–370
Richardson JD, Vasko MR (2002) Cellular mechanisms of neurogenic inflammation. J Pharmacol Exp Ther 302(3):839–845
Edwards JG (2014) TRPV1 in the central nervous system: synaptic plasticity, function, and pharmacological implications. Prog Drug Res 68:77–104
Maione S, Cristino L, Migliozzi AL, Georgiou AL, Starowicz K, Salt TE, Di MV (2009) TRPV1 channels control synaptic plasticity in the developing superior colliculus. J Physiol 587(Pt 11):2521–2535
Matta JA, Ahern GP (2011) TRPV1 and synaptic transmission. Curr Pharm Biotechnol 12(1):95–101
Song J, Lee JH, Lee SH, Park KA, Lee WT, Lee JE (2013) TRPV1 activation in primary cortical neurons induces calcium-dependent programmed cell death. Exp Neurobiol 22(1):51–57
Shirakawa H, Yamaoka T, Sanpei K, Sasaoka H, Nakagawa T, Kaneko S (2008) TRPV1 stimulation triggers apoptotic cell death of rat cortical neurons. Biochem Biophys Res Commun 377(4):1211–1215
Ghazizadeh V, Naziroglu M (2014) Electromagnetic radiation (Wi-Fi) and epilepsy induce calcium entry and apoptosis through activation of TRPV1 channel in hippocampus and dorsal root ganglion of rats. Metab Brain Dis 29(3):787–799
Ovey IS, Naziroglu M (2015) Homocysteine and cytosolic GSH depletion induce apoptosis and oxidative toxicity through cytosolic calcium overload in the hippocampus of aged mice: involvement of TRPM2 and TRPV1 channels. Neuroscience 284:225–233
Starowicz K, Cristino L, Di MV (2008) TRPV1 receptors in the central nervous system: potential for previously unforeseen therapeutic applications. Curr Pharm Des 14(1):42–54
Alawi K, Keeble J (2010) The paradoxical role of the transient receptor potential vanilloid 1 receptor in inflammation. Pharmacol Ther 125(2):181–195
Fernandes ES, Fernandes MA, Keeble JE (2012) The functions of TRPA1 and TRPV1: moving away from sensory nerves. Br J Pharmacol 166(2):510–521
Denda M, Tsutsumi M (2011) Roles of transient receptor potential proteins (TRPs) in epidermal keratinocytes. Adv Exp Med Biol 704:847–860
Miyazaki A, Ohkubo T, Hatta M, Ishikawa H, Yamazaki J (2015) Integrin alpha6beta4 and TRPV1 channel coordinately regulate directional keratinocyte migration. Biochem Biophys Res Commun 458(1):161–167
Lee YM, Kang SM, Chung JH (2012) The role of TRPV1 channel in aged human skin. J Dermatol Sci 65(2):81–85
Li S, Bode AM, Zhu F, Liu K, Zhang J, Kim MO, Reddy K, Zykova T, Ma WY, Carper AL, Langfald AK, Dong Z (2011) TRPV1-antagonist AMG9810 promotes mouse skin tumorigenesis through EGFR/Akt signaling. Carcinogenesis 32(5):779–785
Lieben L, Carmeliet G (2012) The involvement of TRP channels in bone homeostasis. Front Endocrinol 3:99
Idris AI, Landao-Bassonga E, Ralston SH (2010) The TRPV1 ion channel antagonist capsazepine inhibits osteoclast and osteoblast differentiation in vitro and ovariectomy induced bone loss in vivo. Bone 46(4):1089–1099
Rossi F, Bellini G, Torella M, Tortora C, Manzo I, Giordano C, Guida F, Luongo L, Papale F, Rosso F, Nobili B, Maione S (2014) The genetic ablation or pharmacological inhibition of TRPV1 signalling is beneficial for the restoration of quiescent osteoclast activity in ovariectomized mice. Br J Pharmacol 171(10):2621–2630
Park U, Vastani N, Guan Y, Raja SN, Koltzenburg M, Caterina MJ (2011) TRP vanilloid 2 knock-out mice are susceptible to perinatal lethality but display normal thermal and mechanical nociception. J Neurosci 31(32):11425–11436
Mercado J, Gordon-Shaag A, Zagotta WN, Gordon SE (2010) Ca2+-dependent desensitization of TRPV2 channels is mediated by hydrolysis of phosphatidylinositol 4,5-bisphosphate. J Neurosci 30:13338–13347
Gordon-Shaag A, Zagotta WN, Gordon SE (2008) Mechanism of Ca2+-dependent desensitization in TRP channels. Channels 2:125–129
Kanzaki M, Zhang YQ, Mashima H, Li L, Shibata H, Kojima I (1999) Translocation of a calcium-permeable cation channel induced by insulin-like growth factor-I. Nat Cell Biol 1:165–170
Cohen MR, Huynh KW, Cawley D, Moiseenkova-Bell VY (2013) Understanding the cellular function of TRPV2 channel through generation of specific monoclonal antibodies. PLoS One 8:e85392
Qin N, Neeper MP, Liu Y, Hutchinson TL, Lubin ML, Flores CM (2008) TRPV2 is activated by cannabidiol and mediates CGRP release in cultured rat dorsal root ganglion neurons. J Neurosci 28(24):6231–6238
Shibasaki K, Murayama N, Ono K, Ishizaki Y, Tominaga M (2010) TRPV2 enhances axon outgrowth through its activation by membrane stretch in developing sensory and motor neurons. J Neurosci 30(13):4601–4612
Mihara H, Boudaka A, Shibasaki K, Yamanaka A, Sugiyama T, Tominaga M (2010) Involvement of TRPV2 activation in intestinal movement through nitric oxide production in mice. J Neurosci 30(49):16536–16544
Aoyagi K, Ohara-Imaizumi M, Nishiwaki C, Nakamichi Y, Nagamatsu S (2010) Insulin/phosphoinositide 3-kinase pathway accelerates the glucose-induced first-phase insulin secretion through TrpV2 recruitment in pancreatic beta-cells. Biochem J 432(2):375–386
Hisanaga E, Nagasawa M, Ueki K, Kulkarni RN, Mori M, Kojima I (2009) Regulation of calcium-permeable TRPV2 channel by insulin in pancreatic beta-cells. Diabetes 58(1):174–184
Pottosin I, Delgado-Enciso I, Bonales-Alatorre E, Nieto-Pescador MG, Moreno-Galindo EG, Dobrovinskaya O (2015) Mechanosensitive Ca(2)(+)-permeable channels in human leukemic cells: pharmacological and molecular evidence for TRPV2. Biochim Biophys Acta 1848(1 Pt A):51–59
Schwarz EC, Wolfs MJ, Tonner S, Wenning AS, Quintana A, Griesemer D, Hoth M (2007) TRP channels in lymphocytes. Handb Exp Pharmacol 179:445–456
Santoni G, Farfariello V, Liberati S, Morelli MB, Nabissi M, Santoni M, Amantini C (2013) The role of transient receptor potential vanilloid type-2 ion channels in innate and adaptive immune responses. Front Immunol 4:34
Zhang D, Spielmann A, Wang L, Ding G, Huang F, Gu Q, Schwarz W (2012) Mast-cell degranulation induced by physical stimuli involves the activation of transient-receptor-potential channel TRPV2. Physiol Res 61(1):113–124
Stokes AJ, Shimoda LM, Koblan-Huberson M, Adra CN, Turner H (2004) A TRPV2-PKA signaling module for transduction of physical stimuli in mast cells. J Exp Med 200(2):137–147
Nagasawa M, Nakagawa Y, Tanaka S, Kojima I (2007) Chemotactic peptide fMetLeuPhe induces translocation of the TRPV2 channel in macrophages. J Cell Physiol 210(3):692–702
Issa CM, Hambly BD, Wang Y, Maleki S, Wang W, Fei J, Bao S (2014) TRPV2 in the development of experimental colitis. Scand J Immunol 80(5):307–312
Entin-Meer M, Levy R, Goryainov P, Landa N, Barshack I, Avivi C, Semo J, Keren G (2014) The transient receptor potential vanilloid 2 cation channel is abundant in macrophages accumulating at the peri-infarct zone and may enhance their migration capacity towards injured cardiomyocytes following myocardial infarction. PLoS One 9(8):e105055
Link TM, Park U, Vonakis BM, Raben DM, Soloski MJ, Caterina MJ (2010) TRPV2 has a pivotal role in macrophage particle binding and phagocytosis. Nat Immunol 11(3):232–239
Morelli MB, Liberati S, Amantini C, Nabiss M, Santoni M, Farfariello V, Santoni G (2013) Expression and function of the transient receptor potential ion channel family in the hematologic malignancies. Curr Mol Pharmacol 6(3):137–148
Liberati S, Morelli MB, Amantini C, Santoni M, Nabissi M, Cardinali C, Santoni G (2014) Advances in transient receptor potential vanilloid-2 channel expression and function in tumor growth and progression. Curr Protein Pept Sci 15(7):732–737
Morelli MB, Nabissi M, Amantini C, Farfariello V, Ricci-Vitiani L, di Martino S, Pallini R, Larocca LM, Caprodossi S, Santoni M, De Maria R, Santoni G (2012) The transient receptor potential vanilloid-2 cation channel impairs glioblastoma stem-like cell proliferation and promotes differentiation. International journal of cancer. J Int Cancer 131(7):E1067–E1077
Nabissi M, Morelli MB, Amantini C, Farfariello V, Ricci-Vitiani L, Caprodossi S, Arcella A, Santoni M, Giangaspero F, De Maria R, Santoni G (2010) TRPV2 channel negatively controls glioma cell proliferation and resistance to Fas-induced apoptosis in ERK-dependent manner. Carcinogenesis 31(5):794–803
Yamada T, Ueda T, Shibata Y, Ikegami Y, Saito M, Ishida Y, Ugawa S, Kohri K, Shimada S (2010) TRPV2 activation induces apoptotic cell death in human T24 bladder cancer cells: a potential therapeutic target for bladder cancer. Urology 76(2):509 e501–509 e507
Liu Q, Wang X (2013) Effect of TRPV2 cation channels on the proliferation, migration and invasion of 5637 bladder cancer cells. Exp Ther Med 6(5):1277–1282
Nabissi M, Morelli MB, Santoni M, Santoni G (2013) Triggering of the TRPV2 channel by cannabidiol sensitizes glioblastoma cells to cytotoxic chemotherapeutic agents. Carcinogenesis 34(1):48–57
Liu G, Xie C, Sun F, Xu X, Yang Y, Zhang T, Deng Y, Wang D, Huang Z, Yang L, Huang S, Wang Q, Liu G, Zhong D, Miao X (2010) Clinical significance of transient receptor potential vanilloid 2 expression in human hepatocellular carcinoma. Cancer Genet Cytogenet 197(1):54–59
Zhou K, Zhang SS, Yan Y, Zhao S (2014) Overexpression of transient receptor potential vanilloid 2 is associated with poor prognosis in patients with esophageal squamous cell carcinoma. Med Oncol 31(7):17
Monet M, Lehen’kyi V, Gackiere F, Firlej V, Vandenberghe M, Roudbaraki M, Gkika D, Pourtier A, Bidaux G, Slomianny C, Delcourt P, Rassendren F, Bergerat JP, Ceraline J, Cabon F, Humez S, Prevarskaya N (2010) Role of cationic channel TRPV2 in promoting prostate cancer migration and progression to androgen resistance. Cancer Res 70(3):1225–1235
Oulidi A, Bokhobza A, Gkika D, Vanden Abeele F, Lehen’kyi V, Ouafik L, Mauroy B, Prevarskaya N (2013) TRPV2 mediates adrenomedullin stimulation of prostate and urothelial cancer cell adhesion, migration and invasion. PLoS One 8(5):e64885
Katanosaka Y, Iwasaki K, Ujihara Y, Takatsu S, Nishitsuji K, Kanagawa M, Sudo A, Toda T, Katanosaka K, Mohri S, Naruse K (2014) TRPV2 is critical for the maintenance of cardiac structure and function in mice. Nat Commun 5:3932
Koch SE, Gao X, Haar L, Jiang M, Lasko VM, Robbins N, Cai W, Brokamp C, Varma P, Tranter M, Liu Y, Ren X, Lorenz JN, Wang HS, Jones WK, Rubinstein J (2012) Probenecid: novel use as a non-injurious positive inotrope acting via cardiac TRPV2 stimulation. J Mol Cell Cardiol 53(1):134–144
Rubinstein J, Lasko VM, Koch SE, Singh VP, Carreira V, Robbins N, Patel AR, Jiang M, Bidwell P, Kranias EG, Jones WK, Lorenz JN (2014) Novel role of transient receptor potential vanilloid 2 in the regulation of cardiac performance. Am J Physiol Heart Circ Physiol 306(4):H574–H584
Iwata Y, Katanosaka Y, Arai Y, Komamura K, Miyatake K, Shigekawa M (2003) A novel mechanism of myocyte degeneration involving the Ca2+-permeable growth factor-regulated channel. J Cell Biol 161(5):957–967
Iwata Y, Katanosaka Y, Arai Y, Shigekawa M, Wakabayashi S (2009) Dominant-negative inhibition of Ca2+ influx via TRPV2 ameliorates muscular dystrophy in animal models. Hum Mol Genet 18(5):824–834
Harisseh R, Chatelier A, Magaud C, Deliot N, Constantin B (2013) Involvement of TRPV2 and SOCE in calcium influx disorder in DMD primary human myotubes with a specific contribution of alpha1-syntrophin and PLC/PKC in SOCE regulation. Am J Physiol Cell Physiol 304(9):C881–C894
Iwata Y, Ohtake H, Suzuki O, Matsuda J, Komamura K, Wakabayashi S (2013) Blockade of sarcolemmal TRPV2 accumulation inhibits progression of dilated cardiomyopathy. Cardiovasc Res 99(4):760–768
Lorin C, Vogeli I, Niggli E (2015) Dystrophic cardiomyopathy: role of TRPV2 channels in stretch-induced cell damage. Cardiovasc Res 106:153–162
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 418:181–186
Bang S, Yoo S, Yang T-J, Cho H, Hwang SW (2010) Farnesyl pyrophosphate is a novel pain-producing molecule via specific activation of TRPV3. J Biol Chem 285:19362–19371
Xiao R, Tang J, Wang C, Colton CK, Tian J, Zhu MX (2008) Calcium plays a central role in the sensitization of TRPV3 channel to repetitive stimulations. J Biol Chem 283:6162–6174
Phelps CB, Wang RR, Choo SS, Gaudet R (2010) Differential regulation of TRPV1, TRPV3, and TRPV4 sensitivity through a conserved binding site on the ankyrin repeat domain. J Biol Chem 285(1):731–740
Saito S, Fukuta N, Shingai R, Tominaga M (2011) Evolution of vertebrate transient receptor potential vanilloid 3 channels: opposite temperature sensitivity between mammals and western clawed frogs. PLoS Genet 7(4):e1002041
Peier AM, Reeve AJ, Andersson DA, Moqrich A, Earley TJ, Hergarden AC, Story GM, Colley S, Hogenesch JB, McIntyre P, Bevan S, Patapoutian A (2002) A heat-sensitive TRP channel expressed in keratinocytes. Science 296(5575):2046–2049
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 307(5714):1468–1472
Huang SM, Li X, Yu Y, Wang J, Caterina MJ (2011) TRPV3 and TRPV4 ion channels are not major contributors to mouse heat sensation. Mol Pain 7:37
Nilius B, Biro T (2013) TRPV3: a ‘more than skinny’ channel. Exp Dermatol 22(7):447–452
Nilius B, Biro T, Owsianik G (2014) TRPV3: time to decipher a poorly understood family member! J Physiol 592(Pt 2):295–304
Huang SM, Lee H, Chung MK, Park U, Yu YY, Bradshaw HB, Coulombe PA, Walker JM, Caterina MJ (2008) Overexpressed transient receptor potential vanilloid 3 ion channels in skin keratinocytes modulate pain sensitivity via prostaglandin E2. J Neurosci 28(51):13727–13737
Masamoto Y, Kawabata F, Fushiki T (2009) Intragastric administration of TRPV1, TRPV3, TRPM8, and TRPA1 agonists modulates autonomic thermoregulation in different manners in mice. Biosci Biotechnol Biochem 73(5):1021–1027
Cheng X, Jin J, Hu L, Shen D, Dong XP, Samie MA, Knoff J, Eisinger B, Liu ML, Huang SM, Caterina MJ, Dempsey P, Michael LE, Dlugosz AA, Andrews NC, Clapham DE, Xu H (2010) TRP channel regulates EGFR signaling in hair morphogenesis and skin barrier formation. Cell 141(2):331–343
Xiao R, Tian J, Tang J, Zhu MX (2008) The TRPV3 mutation associated with the hairless phenotype in rodents is constitutively active. Cell Calcium 43(4):334–343
Nilius B, Voets T (2013) The puzzle of TRPV4 channelopathies. EMBO Rep 14(2):152–163
Garcia-Elias A, Mrkonjic S, Jung C, Pardo-Pastor C, Vicente R, Valverde MA (2014) The TRPV4 channel. Handb Exp Pharmacol 222:293–319
Güler 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 22:6408–6414
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 277:47044–47051
Garcia-Elias A, Mrkonjic S, Pardo-Pastor C, Inada H, Hellmich UA, Rubio-Moscardo F, Plata C, Gaudet R, Vicente R, Valverde MA (2013) Phosphatidylinositol-4,5-biphosphate-dependent rearrangement of TRPV4 cytosolic tails enables channel activation by physiological stimuli. Proc Natl Acad Sci U S A 110(23):9553–9558
Vriens J, Owsianik G, Janssens A, Voets T, Nilius B (2007) Determinants of 4 alpha-phorbol sensitivity in transmembrane domains 3 and 4 of the cation channel TRPV4. J Biol Chem 282:12796–12803
Vriens J, Watanabe H, Janssens A, Droogmans G, Voets T, Nilius B (2004) Cell swelling, heat, and chemical agonists use distinct pathways for the activation of the cation channel TRPV4. Proc Natl Acad Sci U S A 101:396–401
Watanabe H, Vriens J, Janssens A, Wondergem R, Droogmans G, Nilius B (2003) Modulation of TRPV4 gating by intra- and extracellular Ca2+. Cell Calcium 33(5–6):489–495
Strotmann R, Semtner M, Kepura F, Plant TD, Schöneberg T (2010) Interdomain interactions control Ca2+-dependent potentiation in the cation channel TRPV4. PLoS One 5:e10580
Alessandri-Haber N, Dina OA, Joseph EK, Reichling D, Levine JD (2006) A transient receptor potential vanilloid 4-dependent mechanism of hyperalgesia is engaged by concerted action of inflammatory mediators. J Neurosci Off J Soc Neurosci 26:3864–3874
Xu F, Satoh E, Iijima T (2003) Protein kinase C-mediated Ca2+ entry in HEK 293 cells transiently expressing human TRPV4. Br J Pharmacol 140:413–421
Everaerts W, Nilius B, Owsianik G (2010) The vanilloid transient receptor potential channel TRPV4: from structure to disease. Prog Biophys Mol Biol 103(1):2–17
Dai J, Cho TJ, Unger S, Lausch E, Nishimura G, Kim OH, Superti-Furga A, Ikegawa S (2010) TRPV4-pathy, a novel channelopathy affecting diverse systems. J Hum Genet 55(7):400–402
Verma P, Kumar A, Goswami C (2010) TRPV4-mediated channelopathies. Channels 4(4):319–328
McNulty AL, Leddy HA, Liedtke W, Guilak F (2015) TRPV4 as a therapeutic target for joint diseases. Naunyn-Schmiedeberg’s Arch Pharmacol 388(4):437–450
Krakow D, Vriens J, Camacho N, Luong P, Deixler H, Funari TL, Bacino CA, Irons MB, Holm IA, Sadler L, Okenfuss EB, Janssens A, Voets T, Rimoin DL, Lachman RS, Nilius B, Cohn DH (2009) Mutations in the gene encoding the calcium-permeable ion channel TRPV4 produce spondylometaphyseal dysplasia, Kozlowski type and metatropic dysplasia. Am J Hum Genet 84(3):307–315
Camacho N, Krakow D, Johnykutty S, Katzman PJ, Pepkowitz S, Vriens J, Nilius B, Boyce BF, Cohn DH (2010) Dominant TRPV4 mutations in nonlethal and lethal metatropic dysplasia. Am J Med Genet Part A 152A(5):1169–1177
Rock MJ, Prenen J, Funari VA, Funari TL, Merriman B, Nelson SF, Lachman RS, Wilcox WR, Reyno S, Quadrelli R, Vaglio A, Owsianik G, Janssens A, Voets T, Ikegawa S, Nagai T, Rimoin DL, Nilius B, Cohn DH (2008) Gain-of-function mutations in TRPV4 cause autosomal dominant brachyolmia. Nat Genet 40(8):999–1003
Weinstein MM, Tompson SW, Chen Y, Lee B, Cohn DH (2014) Mice expressing mutant Trpv4 recapitulate the human TRPV4 disorders. J Bone Mineral Res 29(8):1815–1822
Lamande SR, Yuan Y, Gresshoff IL, Rowley L, Belluoccio D, Kaluarachchi K, Little CB, Botzenhart E, Zerres K, Amor DJ, Cole WG, Savarirayan R, McIntyre P, Bateman JF (2011) Mutations in TRPV4 cause an inherited arthropathy of hands and feet. Nat Genet 43(11):1142–1146
Clark AL, Votta BJ, Kumar S, Liedtke W, Guilak F (2010) Chondroprotective role of the osmotically sensitive ion channel transient receptor potential vanilloid 4: age- and sex-dependent progression of osteoarthritis in Trpv4-deficient mice. Arthritis Rheum 62(10):2973–2983
Masuyama R, Vriens J, Voets T, Karashima Y, Owsianik G, Vennekens R, Lieben L, Torrekens S, Moermans K, Vanden Bosch A, Bouillon R, Nilius B, Carmeliet G (2008) TRPV4-mediated calcium influx regulates terminal differentiation of osteoclasts. Cell Metab 8(3):257–265
O’Conor CJ, Leddy HA, Benefield HC, Liedtke WB, Guilak F (2014) TRPV4-mediated mechanotransduction regulates the metabolic response of chondrocytes to dynamic loading. Proc Natl Acad Sci U S A 111(4):1316–1321
Fecto F, Shi Y, Huda R, Martina M, Siddique T, Deng HX (2011) Mutant TRPV4-mediated toxicity is linked to increased constitutive function in axonal neuropathies. J Biol Chem 286(19):17281–17291
Klein CJ, Shi Y, Fecto F, Donaghy M, Nicholson G, McEntagart ME, Crosby AH, Wu Y, Lou H, McEvoy KM, Siddique T, Deng HX, Dyck PJ (2011) TRPV4 mutations and cytotoxic hypercalcemia in axonal Charcot-Marie-Tooth neuropathies. Neurology 76(10):887–894
Mederos y Schnitzler M, Waring J, Gudermann T, Chubanov V (2008) Evolutionary determinants of divergent calcium selectivity of TRPM channels. FASEB J 22(5):1540–1551
Togashi K, Hara Y, Tominaga T, Higashi T, Konishi Y, Mori Y, Tominaga M (2006) TRPM2 activation by cyclic ADP-ribose at body temperature is involved in insulin secretion. EMBO J 25(9):1804–1815
Faouzi M, Penner R (2014) Trpm2. Handb Exp Pharmacol 222:403–426
Du J, Xie J, Yue L (2009) Intracellular calcium activates TRPM2 and its alternative spliced isoforms. Proc Natl Acad Sci U S A 106(17):7239–7244
Tong Q, Zhang W, Conrad K, Mostoller K, Cheung JY, Peterson BZ, Miller BA (2006) Regulation of the transient receptor potential channel TRPM2 by the Ca2+ sensor calmodulin. J Biol Chem 281(14):9076–9085
Uchida K, Tominaga M (2011) TRPM2 modulates insulin secretion in pancreatic beta-cells. Islets 3(4):209–211
Hecquet CM, Malik AB (2009) Role of H(2)O(2)-activated TRPM2 calcium channel in oxidant-induced endothelial injury. Thromb Haemost 101(4):619–625
Starkus J, Beck A, Fleig A, Penner R (2007) Regulation of TRPM2 by extra- and intracellular calcium. J Gen Physiol 130(4):427–440
Knowles H, Li Y, Perraud AL (2013) The TRPM2 ion channel, an oxidative stress and metabolic sensor regulating innate immunity and inflammation. Immunol Res 55(1–3):241–248
Sumoza-Toledo A, Lange I, Cortado H, Bhagat H, Mori Y, Fleig A, Penner R, Partida-Sanchez S (2011) Dendritic cell maturation and chemotaxis is regulated by TRPM2-mediated lysosomal Ca2+ release. FASEB J 25(10):3529–3542
Takahashi N, Kozai D, Kobayashi R, Ebert M, Mori Y (2011) Roles of TRPM2 in oxidative stress. Cell Calcium 50(3):279–287
Yamamoto S, Shimizu S, Kiyonaka S, Takahashi N, Wajima T, Hara Y, Negoro T, Hiroi T, Kiuchi Y, Okada T, Kaneko S, Lange I, Fleig A, Penner R, Nishi M, Takeshima H, Mori Y (2008) TRPM2-mediated Ca2+influx induces chemokine production in monocytes that aggravates inflammatory neutrophil infiltration. Nat Med 14(7):738–747
Oda S, Uchida K, Wang X, Lee J, Shimada Y, Tominaga M, Kadowaki M (2013) TRPM2 contributes to antigen-stimulated Ca(2)(+) influx in mucosal mast cells. Pflugers Arch – Eur J Physiol 465(7):1023–1030
Fonfria E, Murdock PR, Cusdin FS, Benham CD, Kelsell RE, McNulty S (2006) Tissue distribution profiles of the human TRPM cation channel family. J Recept Signal Transduct Res 26(3):159–178
Vandewauw I, Owsianik G, Voets T (2013) Systematic and quantitative mRNA expression analysis of TRP channel genes at the single trigeminal and dorsal root ganglion level in mouse. BMC Neurosci 14:21
Naziroglu M, Ozgul C (2013) Vitamin E modulates oxidative stress and protein kinase C activator (PMA)-induced TRPM2 channel gate in dorsal root ganglion of rats. J Bioenerg Biomembr 45(6):541–549
Xu C, Macciardi F, Li PP, Yoon IS, Cooke RG, Hughes B, Parikh SV, McIntyre RS, Kennedy JL, Warsh JJ (2006) Association of the putative susceptibility gene, transient receptor potential protein melastatin type 2, with bipolar disorder. Am J Med Genet Part B Neuropsychiatr Genet 141B(1):36–43
Kaneko S, Kawakami S, Hara Y, Wakamori M, Itoh E, Minami T, Takada Y, Kume T, Katsuki H, Mori Y, Akaike A (2006) A critical role of TRPM2 in neuronal cell death by hydrogen peroxide. J Pharmacol Sci 101(1):66–76
Hermosura MC, Garruto RM (2007) TRPM7 and TRPM2-candidate susceptibility genes for Western Pacific ALS and PD? Biochim Biophys Acta 1772(8):822–835
Zhang E, Liao P (2015) Brain transient receptor potential channels and stroke. J Neurosci Res 93(8):1165–1183
Amina S, Hashii M, Ma WJ, Yokoyama S, Lopatina O, Liu HX, Islam MS, Higashida H (2010) Intracellular calcium elevation induced by extracellular application of cyclic-ADP-ribose or oxytocin is temperature-sensitive in rodent NG108-15 neuronal cells with or without exogenous expression of human oxytocin receptors. J Neuroendocrinol 22(5):460–466
Lange I, Yamamoto S, Partida-Sanchez S, Mori Y, Fleig A, Penner R (2009) TRPM2 functions as a lysosomal Ca2+-release channel in beta cells. Sci Signal 2(71):ra23
Zhang Z, Zhang W, Jung DY, Ko HJ, Lee Y, Friedline RH, Lee E, Jun J, Ma Z, Kim F, Tsitsilianos N, Chapman K, Morrison A, Cooper MP, Miller BA, Kim JK (2012) TRPM2 Ca2+ channel regulates energy balance and glucose metabolism. Am J Physiol Endocrinol Metab 302(7):E807–E816
Uchida K, Tominaga M (2014) The role of TRPM2 in pancreatic beta-cells and the development of diabetes. Cell Calcium 56(5):332–339
Oberwinkler J, Philipp SE (2014) Trpm3. Handb Exp Pharmacol 222:427–459
Holendova B, Grycova L, Jirku M, Teisinger J (2012) PtdIns(4,5)P2 interacts with CaM binding domains on TRPM3 N-terminus. Channels 6(6):479–482
Lee N, Chen J, Sun L, Wu S, Gray KR, Rich A, Huang M, Lin JH, Feder JN, Janovitz EB, Levesque PC, Blanar MA (2003) Expression and characterization of human transient receptor potential melastatin 3 (hTRPM3). J Biol Chem 278(23):20890–20897
Oberwinkler J, Lis A, Giehl KM, Flockerzi V, Philipp SE (2005) Alternative splicing switches the divalent cation selectivity of TRPM3 channels. J Biol Chem 280(23):22540–22548
Thiel G, Muller I, Rossler OG (2013) Signal transduction via TRPM3 channels in pancreatic beta-cells. J Mol Endocrinol 50(3):R75–R83
Naylor J, Li J, Milligan CJ, Zeng F, Sukumar P, Hou B, Sedo A, Yuldasheva N, Majeed Y, Beri D, Jiang S, Seymour VA, McKeown L, Kumar B, Harteneck C, O’Regan D, Wheatcroft SB, Kearney MT, Jones C, Porter KE, Beech DJ (2010) Pregnenolone sulphate- and cholesterol-regulated TRPM3 channels coupled to vascular smooth muscle secretion and contraction. Circ Res 106(9):1507–1515
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(3):482–494
Gonzales AL, Amberg GC, Earley S (2010) Ca2+ release from the sarcoplasmic reticulum is required for sustained TRPM4 activity in cerebral artery smooth muscle cells. Am J Physiol Cell Physiol 299(2):C279–C288
McHugh D, Flemming R, Xu S-Z, Perraud A-L, Beech DJ (2003) Critical intracellular Ca2+ dependence of transient receptor potential melastatin 2 (TRPM2) cation channel activation. J Biol Chem 278:11002–11006
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(7070):1022–1025
Mathar I, Jacobs G, Kecskes M, Menigoz A, Philippaert K, Vennekens R (2014) Trpm4. Handb Exp Pharmacol 222:461–487
Nilius B, Mahieu F, Prenen J, Janssens A, Owsianik G, Vennekens R, Voets T (2006) The Ca2+-activated cation channel TRPM4 is regulated by phosphatidylinositol 4,5-biphosphate. EMBO J 25(3):467–478
Crnich R, Amberg GC, Leo MD, Gonzales AL, Tamkun MM, Jaggar JH, Earley S (2010) Vasoconstriction resulting from dynamic membrane trafficking of TRPM4 in vascular smooth muscle cells. Am J Physiol Cell Physiol 299(3):C682–C694
Barbet G, Demion M, Moura IC, Serafini N, Leger T, Vrtovsnik F, Monteiro RC, Guinamard R, Kinet JP, Launay P (2008) The calcium-activated nonselective cation channel TRPM4 is essential for the migration but not the maturation of dendritic cells. Nat Immunol 9(10):1148–1156
Vennekens R, Olausson J, Meissner M, Bloch W, Mathar I, Philipp SE, Schmitz F, Weissgerber P, Nilius B, Flockerzi V, Freichel M (2007) Increased IgE-dependent mast cell activation and anaphylactic responses in mice lacking the calcium-activated nonselective cation channel TRPM4. Nat Immunol 8(3):312–320
Serafini N, Dahdah A, Barbet G, Demion M, Attout T, Gautier G, Arcos-Fajardo M, Souchet H, Jouvin MH, Vrtovsnik F, Kinet JP, Benhamou M, Monteiro RC, Launay P (2012) The TRPM4 channel controls monocyte and macrophage, but not neutrophil, function for survival in sepsis. J Immunol 189(7):3689–3699
Weber KS, Hildner K, Murphy KM, Allen PM (2010) Trpm4 differentially regulates Th1 and Th2 function by altering calcium signaling and NFAT localization. J Immunol 185(5):2836–2846
Schattling B, Steinbach K, Thies E, Kruse M, Menigoz A, Ufer F, Flockerzi V, Bruck W, Pongs O, Vennekens R, Kneussel M, Freichel M, Merkler D, Friese MA (2012) TRPM4 cation channel mediates axonal and neuronal degeneration in experimental autoimmune encephalomyelitis and multiple sclerosis. Nat Med 18(12):1805–1811
Gerzanich V, Woo SK, Vennekens R, Tsymbalyuk O, Ivanova S, Ivanov A, Geng Z, Chen Z, Nilius B, Flockerzi V, Freichel M, Simard JM (2009) De novo expression of Trpm4 initiates secondary hemorrhage in spinal cord injury. Nat Med 15(2):185–191
Nelson P, Ngoc Tran TD, Zhang H, Zolochevska O, Figueiredo M, Feng JM, Gutierrez DL, Xiao R, Yao S, Penn A, Yang LJ, Cheng H (2013) Transient receptor potential melastatin 4 channel controls calcium signals and dental follicle stem cell differentiation. Stem Cells 31(1):167–177
Nelson PL, Zolochevska O, Figueiredo ML, Soliman A, Hsu WH, Feng JM, Zhang H, Cheng H (2011) Regulation of Ca(2+)-entry in pancreatic alpha-cell line by transient receptor potential melastatin 4 plays a vital role in glucagon release. Mol Cell Endocrinol 335(2):126–134
Kruse M, Pongs O (2014) TRPM4 channels in the cardiovascular system. Curr Opin Pharmacol 15:68–73
Gonzales AL, Earley S (2012) Endogenous cytosolic Ca(2+) buffering is necessary for TRPM4 activity in cerebral artery smooth muscle cells. Cell Calcium 51(1):82–93
Earley S (2013) TRPM4 channels in smooth muscle function. Pflugers Arch – Eur J Physiol 465(9):1223–1231
Kruse M, Schulze-Bahr E, Corfield V, Beckmann A, Stallmeyer B, Kurtbay G, Ohmert I, Schulze-Bahr E, Brink P, Pongs O (2009) Impaired endocytosis of the ion channel TRPM4 is associated with human progressive familial heart block type I. J Clin Invest 119(9):2737–2744
Brink AJ (2009) Breaking new ground in research. Cardiovasc J Afr 20(6):335
Stallmeyer B, Zumhagen S, Denjoy I, Duthoit G, Hebert JL, Ferrer X, Maugenre S, Schmitz W, Kirchhefer U, Schulze-Bahr E, Guicheney P, Schulze-Bahr E (2012) Mutational spectrum in the Ca(2+) – activated cation channel gene TRPM4 in patients with cardiac conductance disturbances. Hum Mutat 33(1):109–117
Liu D, Liman ER (2003) Intracellular Ca2+ and the phospholipid PIP2 regulate the taste transduction ion channel TRPM5. Proc Natl Acad Sci U S A 100(25):15160–15165
Zhang Z, Zhao Z, Margolskee R, Liman E (2007) The transduction channel TRPM5 is gated by intracellular calcium in taste cells. J Neurosci Off J Soc Neurosci 27:5777–5786
Ullrich ND, Voets T, Prenen J, Vennekens R, Talavera K, Droogmans G, Nilius B (2005) Comparison of functional properties of the Ca2+-activated cation channels TRPM4 and TRPM5 from mice. Cell Calcium 37:267–278
Palmer RK, Lunn CA (2013) TRP channels as targets for therapeutic intervention in obesity: focus on TRPV1 and TRPM5. Curr Top Med Chem 13(3):247–257
Lin W, Margolskee R, Donnert G, Hell SW, Restrepo D (2007) Olfactory neurons expressing transient receptor potential channel M5 (TRPM5) are involved in sensing semiochemicals. Proc Natl Acad Sci U S A 104(7):2471–2476
Perez CA, Huang L, Rong M, Kozak JA, Preuss AK, Zhang H, Max M, Margolskee RF (2002) A transient receptor potential channel expressed in taste receptor cells. Nat Neurosci 5(11):1169–1176
Colsoul B, Schraenen A, Lemaire K, Quintens R, Van Lommel L, Segal A, Owsianik G, Talavera K, Voets T, Margolskee RF, Kokrashvili Z, Gilon P, Nilius B, Schuit FC, Vennekens R (2010) Loss of high-frequency glucose-induced Ca2+ oscillations in pancreatic islets correlates with impaired glucose tolerance in Trpm5-/- mice. Proc Natl Acad Sci U S A 107(11):5208–5213
Brixel LR, Monteilh-Zoller MK, Ingenbrandt CS, Fleig A, Penner R, Enklaar T, Zabel BU, Prawitt D (2010) TRPM5 regulates glucose-stimulated insulin secretion. Pflugers Arch – Eur J Physiol 460(1):69–76
Ketterer C, Mussig K, Heni M, Dudziak K, Randrianarisoa E, Wagner R, Machicao F, Stefan N, Holst JJ, Fritsche A, Haring HU, Staiger H (2011) Genetic variation within the TRPM5 locus associates with prediabetic phenotypes in subjects at increased risk for type 2 diabetes. Metab Clin Exp 60(9):1325–1333
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(7150):204–208
Colburn RW, Lubin ML, Stone DJ Jr, Wang Y, Lawrence D, D’Andrea MR, Brandt MR, Liu Y, Flores CM, Qin N (2007) Attenuated cold sensitivity in TRPM8 null mice. Neuron 54(3):379–386
Dhaka A, Murray AN, Mathur J, Earley TJ, Petrus MJ, Patapoutian A (2007) TRPM8 is required for cold sensation in mice. Neuron 54(3):371–378
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 108:705–715
McKemy DD, Neuhausser WM, Julius D (2002) Identification of a cold receptor reveals a general role for TRP channels in thermosensation. Nature 416(6876):52–58
Yudin Y, Rohacs T (2012) Regulation of TRPM8 channel activity. Mol Cell Endocrinol 353(1–2):68–74
Sarria I, Gu J (2010) Menthol response and adaptation in nociceptive-like and nonnociceptive-like neurons: role of protein kinases. Mol Pain 6:47
Sarria I, Ling J, Zhu MX, Gu JG (2011) TRPM8 acute desensitization is mediated by calmodulin and requires PIP(2): distinction from tachyphylaxis. J Neurophysiol 106(6):3056–3066
Rohacs T, Lopes CM, Michailidis I, Logothetis DE (2005) PI(4,5)P2 regulates the activation and desensitization of TRPM8 channels through the TRP domain. Nat Neurosci 8(5):626–634
Liu B, Qin F (2005) Functional control of cold- and menthol-sensitive TRPM8 ion channels by phosphatidylinositol 4,5-bisphosphate. J Neurosci 25(7):1674–1681
Daniels RL, Takashima Y, McKemy DD (2009) Activity of the neuronal cold sensor TRPM8 is regulated by phospholipase C via the phospholipid phosphoinositol 4,5-bisphosphate. J Biol Chem 284(3):1570–1582
Yudin Y, Lukacs V, Cao C, Rohacs T (2011) Decrease in phosphatidylinositol 4,5-bisphosphate levels mediates desensitization of the cold sensor TRPM8 channels. J Physiol 589:6007–6027
Bavencoffe A, Gkika D, Kondratskyi A, Beck B, Borowiec AS, Bidaux G, Busserolles J, Eschalier A, Shuba Y, Skryma R, Prevarskaya N (2010) The transient receptor potential channel TRPM8 is inhibited via the alpha 2A adrenoreceptor signaling pathway. J Biol Chem 285(13):9410–9419
De Petrocellis L, Starowicz K, Moriello AS, Vivese M, Orlando P, Di Marzo V (2007) Regulation of transient receptor potential channels of melastatin type 8 (TRPM8): effect of cAMP, cannabinoid CB1 receptors and endovanilloids. Exp Cell Res 313:1911–1920
Linte RM, Ciobanu C, Reid G, Babes A (2007) Desensitization of cold- and menthol-sensitive rat dorsal root ganglion neurones by inflammatory mediators. Exp Brain Res 178(1):89–98
Abe J, Hosokawa H, Sawada Y, Matsumura K, Kobayashi S (2006) Ca2+-dependent PKC activation mediates menthol-induced desensitization of transient receptor potential M8. Neurosci Lett 397(1–2):140–144
Premkumar LS, Raisinghani M, Pingle SC, Long C, Pimentel F (2005) Downregulation of transient receptor potential melastatin 8 by protein kinase C-mediated dephosphorylation. J Neurosci 25(49):11322–11329
Malkia A, Morenilla-Palao C, Viana F (2011) The emerging pharmacology of TRPM8 channels: hidden therapeutic potential underneath a cold surface. Curr Pharm Biotechnol 12(1):54–67
Bidaux G, Flourakis M, Thebault S, Zholos A, Beck B, Gkika D, Roudbaraki M, Bonnal JL, Mauroy B, Shuba Y, Skryma R, Prevarskaya N (2007) Prostate cell differentiation status determines transient receptor potential melastatin member 8 channel subcellular localization and function. J Clin Invest 117(6):1647–1657
Thebault S, Lemonnier L, Bidaux G, Flourakis M, Bavencoffe A, Gordienko D, Roudbaraki M, Delcourt P, Panchin Y, Shuba Y, Skryma R, Prevarskaya N (2005) Novel role of cold/menthol-sensitive transient receptor potential melastatine family member 8 (TRPM8) in the activation of store-operated channels in LNCaP human prostate cancer epithelial cells. J Biol Chem 280(47):39423–39435
Zhang L, Barritt GJ (2006) TRPM8 in prostate cancer cells: a potential diagnostic and prognostic marker with a secretory function? Endocr Relat Cancer 13(1):27–38
Flourakis M, Prevarskaya N (2009) Insights into Ca2+ homeostasis of advanced prostate cancer cells. Biochim Biophys Acta 1793(6):1105–1109
Mergler S, Derckx R, Reinach PS, Garreis F, Bohm A, Schmelzer L, Skosyrski S, Ramesh N, Abdelmessih S, Polat OK, Khajavi N, Riechardt AI (2014) Calcium regulation by temperature-sensitive transient receptor potential channels in human uveal melanoma cells. Cell Signal 26(1):56–69
Yamamura H, Ugawa S, Ueda T, Morita A, Shimada S (2008) TRPM8 activation suppresses cellular viability in human melanoma. Am J Physiol Cell Physiol 295(2):C296–C301
Mergler S, Strowski MZ, Kaiser S, Plath T, Giesecke Y, Neumann M, Hosokawa H, Kobayashi S, Langrehr J, Neuhaus P, Plockinger U, Wiedenmann B, Grotzinger C (2007) Transient receptor potential channel TRPM8 agonists stimulate calcium influx and neurotensin secretion in neuroendocrine tumor cells. Neuroendocrinology 85(2):81–92
Wondergem R, Ecay TW, Mahieu F, Owsianik G, Nilius B (2008) HGF/SF and menthol increase human glioblastoma cell calcium and migration. Biochem Biophys Res Commun 372(1):210–215
Cucu D, Chiritoiu G, Petrescu S, Babes A, Stanica L, Duda DG, Horii A, Dima SO, Popescu I (2014) Characterization of functional transient receptor potential melastatin 8 channels in human pancreatic ductal adenocarcinoma cells. Pancreas 43(5):795–800
Eid SR, Cortright DN (2009) Transient receptor potential channels on sensory nerves. Handb Exp Pharmacol 194:261–281
Levine JD, Alessandri-Haber N (2007) TRP channels: targets for the relief of pain. Biochim Biophys Acta 1772(8):989–1003
Chung MK, Jung SJ, Oh SB (2011) Role of TRP channels in pain sensation. Adv Exp Med Biol 704:615–636
Almaraz L, Manenschijn JA, de la Pena E, Viana F (2014) Trpm8. Handb Exp Pharmacol 222:547–579
Proudfoot CJ, Garry EM, Cottrell DF, Rosie R, Anderson H, Robertson DC, Fleetwood-Walker SM, Mitchell R (2006) Analgesia mediated by the TRPM8 cold receptor in chronic neuropathic pain. Curr Biol 16(16):1591–1605
Knowlton WM, Daniels RL, Palkar R, McCoy DD, McKemy DD (2011) Pharmacological blockade of TRPM8 ion channels alters cold and cold pain responses in mice. PLoS One 6(9):e25894
Zuo X, Ling JX, Xu GY, Gu JG (2013) Operant behavioral responses to orofacial cold stimuli in rats with chronic constrictive trigeminal nerve injury: effects of menthol and capsazepine. Mol Pain 9:28
Xing H, Chen M, Ling J, Tan W, Gu JG (2007) TRPM8 mechanism of cold allodynia after chronic nerve injury. J Neurosci 27(50):13680–13690
Kurose M, Meng ID (2013) Dry eye modifies the thermal and menthol responses in rat corneal primary afferent cool cells. J Neurophysiol 110(2):495–504
Parra A, Madrid R, Echevarria D, del Olmo S, Morenilla-Palao C, Acosta MC, Gallar J, Dhaka A, Viana F, Belmonte C (2010) Ocular surface wetness is regulated by TRPM8-dependent cold thermoreceptors of the cornea. Nat Med 16(12):1396–1399
Lashinger ES, Steiginga MS, Hieble JP, Leon LA, Gardner SD, Nagilla R, Davenport EA, Hoffman BE, Laping NJ, Su X (2008) AMTB, a TRPM8 channel blocker: evidence in rats for activity in overactive bladder and painful bladder syndrome. Am J Physiol Renal Physiol 295(3):F803–F810
Mukerji G, Yiangou Y, Corcoran SL, Selmer IS, Smith GD, Benham CD, Bountra C, Agarwal SK, Anand P (2006) Cool and menthol receptor TRPM8 in human urinary bladder disorders and clinical correlations. BMC Urol 6:6
Yoshida T, Inoue R, Morii T, Takahashi N, Yamamoto S, Hara Y, Tominaga M, Shimizu S, Sato Y, Mori Y (2006) Nitric oxide activates TRP channels by cysteine S-nitrosylation. Nat Chem Biol 2:596–607
Flemming PK, Dedman AM, Xu S-Z, Li J, Zeng F, Naylor J, Benham CD, Bateson AN, Muraki K, Beech DJ (2006) Sensing of lysophospholipids by TRPC5 calcium channel. J Biol Chem 281:4977–4982
Zhu MH, Chae M, Kim HJ, Lee YM, Kim MJ, Jin NG, Yang DK, So I, Kim KW (2005) Desensitization of canonical transient receptor potential channel 5 by protein kinase C. Am J Physiol Cell Physiol 289(3):C591–C600
Kinoshita-Kawada M, Tang J, Xiao R, Kaneko S, Foskett JK, Zhu MX (2005) Inhibition of TRPC5 channels by Ca2+-binding protein 1 in Xenopus oocytes. Pflügers Arch 450:345–354
Sung TS, Jeon JP, Kim BJ, Hong C, Kim SY, Kim J, Jeon JH, Kim HJ, Suh CK, Kim SJ, So I (2011) Molecular determinants of PKA-dependent inhibition of TRPC5 channel. Am J Physiol Cell Physiol 301:C823–C832
Zholos AV (2014) Trpc5. Handb Exp Pharmacol 222:129–156
Faber ES, Sedlak P, Vidovic M, Sah P (2006) Synaptic activation of transient receptor potential channels by metabotropic glutamate receptors in the lateral amygdala. Neuroscience 137(3):781–794
von Bohlen Und Halbach O, Hinz U, Unsicker K, Egorov AV (2005) Distribution of TRPC1 and TRPC5 in medial temporal lobe structures of mice. Cell Tissue Res 322(2):201–206
De March Z, Giampa C, Patassini S, Bernardi G, Fusco FR (2006) Cellular localization of TRPC5 in the substantia nigra of rat. Neurosci Lett 402(1–2):35–39
Greka A, Navarro B, Oancea E, Duggan A, Clapham DE (2003) TRPC5 is a regulator of hippocampal neurite length and growth cone morphology. Nat Neurosci 6(8):837–845
He Z, Jia C, Feng S, Zhou K, Tai Y, Bai X, Wang Y (2012) TRPC5 channel is the mediator of neurotrophin-3 in regulating dendritic growth via CaMKIIalpha in rat hippocampal neurons. J Neurosci 32(27):9383–9395
Gomis A, Soriano S, Belmonte C, Viana F (2008) Hypoosmotic- and pressure-induced membrane stretch activate TRPC5 channels. J Physiol 586(Pt 23):5633–5649
Min J-W, Liu W-H, He X-H, Peng B-W (2013) Different types of toxins targeting TRPV1 in pain. Toxicon 71:66–75
Zygmunt PM, Hogestatt ED (2014) Trpa1. Handb Exp Pharmacol 222:583–630
Hinman A, H-h C, Bautista DM, Julius D (2006) TRP channel activation by reversible covalent modification. Proc Natl Acad Sci 103:19564–19568
Macpherson LJ, Dubin AE, Evans MJ, Marr F, Schultz PG, Cravatt BF, Patapoutian A (2007) Noxious compounds activate TRPA1 ion channels through covalent modification of cysteines. Nature 445:541–545
Gracheva EO, Ingolia NT, Kelly YM, Cordero-Morales JF, Hollopeter G, Chesler AT, Sánchez EE, Perez JC, Weissman JS, Julius D (2010) Molecular basis of infrared detection by snakes. Nature 464:1006–1011
Moparthi L, Survery S, Kreir M, Simonsen C, Kjellbom P, Högestätt 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 111:16901–16906
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 4:2501
Hamada FN, Rosenzweig M, Kang K, Pulver SR, Ghezzi A, Jegla TJ, Garrity PA (2008) An internal thermal sensor controlling temperature preference in Drosophila. Nature 454:217–220
Dai Y, Wang S, Tominaga M, Yamamoto S, Fukuoka T, Higashi T, Kobayashi K, Obata K, Yamanaka H, Noguchi K (2007) Sensitization of TRPA1 by PAR2 contributes to the sensation of inflammatory pain. J Clin Investig 117:1979–1987
Wang S, Dai Y, Fukuoka T, Yamanaka H, Kobayashi K, Obata K, Cui X, Tominaga M, Noguchi K (2008) Phospholipase C and protein kinase A mediate bradykinin sensitization of TRPA1: a molecular mechanism of inflammatory pain. Brain 131:1241–1251
Schmidt M, Dubin AE, Petrus MJ, Earley TJ, Patapoutian A (2009) Nociceptive signals induce trafficking of TRPA1 to the plasma membrane. Neuron 64(4):498–509
Wang YY, Chang RB, Waters HN, McKemy DD, Liman ER (2008) The nociceptor Ion channel TRPA1 is potentiated and inactivated by permeating calcium ions. J Biol Chem 283:32691–32703
Nassini R, Materazzi S, Benemei S, Geppetti P (2014) The TRPA1 channel in inflammatory and neuropathic pain and migraine. Rev Physiol Biochem Pharmacol 167:1–43
Andrade EL, Meotti FC, Calixto JB (2012) TRPA1 antagonists as potential analgesic drugs. Pharmacol Ther 133(2):189–204
Sawada Y, Hosokawa H, Hori A, Matsumura K, Kobayashi S (2007) Cold sensitivity of recombinant TRPA1 channels. Brain Res 1160:39–46
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 U S A 106(4):1273–1278
Kremeyer B, Lopera F, Cox JJ, Momin A, Rugiero F, Marsh S, Woods CG, Jones NG, Paterson KJ, Fricker FR, Villegas A, Acosta N, Pineda-Trujillo NG, Ramirez JD, Zea J, Burley MW, Bedoya G, Bennett DL, Wood JN, Ruiz-Linares A (2010) A gain-of-function mutation in TRPA1 causes familial episodic pain syndrome. Neuron 66(5):671–680
Patapoutian A, Macpherson L (2006) Channeling pain. Nat Med 12(5):506–507
Hjerling-Leffler J, Alqatari M, Ernfors P, Koltzenburg M (2007) Emergence of functional sensory subtypes as defined by transient receptor potential channel expression. J Neurosci 27(10):2435–2443
Kim YS, Son JY, Kim TH, Paik SK, Dai Y, Noguchi K, Ahn DK, Bae YC (2010) Expression of transient receptor potential ankyrin 1 (TRPA1) in the rat trigeminal sensory afferents and spinal dorsal horn. J Comp Neurol 518(5):687–698
Kunkler PE, Ballard CJ, Oxford GS, Hurley JH (2011) TRPA1 receptors mediate environmental irritant-induced meningeal vasodilatation. Pain 152(1):38–44
Pozsgai G, Bodkin JV, Graepel R, Bevan S, Andersson DA, Brain SD (2010) Evidence for the pathophysiological relevance of TRPA1 receptors in the cardiovascular system in vivo. Cardiovasc Res 87(4):760–768
Engel MA, Leffler A, Niedermirtl F, Babes A, Zimmermann K, Filipovic MR, Izydorczyk I, Eberhardt M, Kichko TI, Mueller-Tribbensee SM, Khalil M, Siklosi N, Nau C, Ivanovic-Burmazovic I, Neuhuber WL, Becker C, Neurath MF, Reeh PW (2011) TRPA1 and substance P mediate colitis in mice. Gastroenterology 141(4):1346–1358
Aubdool AA, Graepel R, Kodji X, Alawi KM, Bodkin JV, Srivastava S, Gentry C, Heads R, Grant AD, Fernandes ES, Bevan S, Brain SD (2014) TRPA1 is essential for the vascular response to environmental cold exposure. Nat Commun 5:5732
Benemei S, Fusi C, Trevisan G, Geppetti P (2014) The TRPA1 channel in migraine mechanism and treatment. Br J Pharmacol 171(10):2552–2567
Wei H, Koivisto A, Saarnilehto M, Chapman H, Kuokkanen K, Hao B, Huang JL, Wang YX, Pertovaara A (2011) Spinal transient receptor potential ankyrin 1 channel contributes to central pain hypersensitivity in various pathophysiological conditions in the rat. Pain 152(3):582–591
da Costa DS, Meotti FC, Andrade EL, Leal PC, Motta EM, Calixto JB (2010) The involvement of the transient receptor potential A1 (TRPA1) in the maintenance of mechanical and cold hyperalgesia in persistent inflammation. Pain 148(3):431–437
Miyakawa T, Terashima Y, Takebayashi T, Tanimoto K, Iwase T, Ogon I, Kobayashi T, Tohse N, Yamashita T (2014) Transient receptor potential ankyrin 1 in spinal cord dorsal horn is involved in neuropathic pain in nerve root constriction rats. Mol Pain 10:58
Andersson DA, Gentry C, Alenmyr L, Killander D, Lewis SE, Andersson A, Bucher B, Galzi JL, Sterner O, Bevan S, Hogestatt ED, Zygmunt PM (2011) TRPA1 mediates spinal antinociception induced by acetaminophen and the cannabinoid Delta(9)-tetrahydrocannabiorcol. Nat Commun 2:551
Shigetomi E, Tong X, Kwan KY, Corey DP, Khakh BS (2012) TRPA1 channels regulate astrocyte resting calcium and inhibitory synapse efficacy through GAT-3. Nat Neurosci 15(1):70–80
Belvisi MG, Dubuis E, Birrell MA (2011) Transient receptor potential A1 channels: insights into cough and airway inflammatory disease. Chest 140(4):1040–1047
Geppetti P, Patacchini R, Nassini R (2014) Transient receptor potential channels and occupational exposure. Curr Opin Allergy Clin Immunol 14(2):77–83
Grace MS, Baxter M, Dubuis E, Birrell MA, Belvisi MG (2014) Transient receptor potential (TRP) channels in the airway: role in airway disease. Br J Pharmacol 171(10):2593–2607
Grace MS, Belvisi MG (2011) TRPA1 receptors in cough. Pulm Pharmacol Ther 24(3):286–288
Schaefer EA, Stohr S, Meister M, Aigner A, Gudermann T, Buech TR (2013) Stimulation of the chemosensory TRPA1 cation channel by volatile toxic substances promotes cell survival of small cell lung cancer cells. Biochem Pharmacol 85(3):426–438
Wilson SR, Gerhold KA, Bifolck-Fisher A, Liu Q, Patel KN, Dong X, Bautista DM (2011) TRPA1 is required for histamine-independent, Mas-related G protein-coupled receptor-mediated itch. Nat Neurosci 14(5):595–602
Liu B, Escalera J, Balakrishna S, Fan L, Caceres AI, Robinson E, Sui A, McKay MC, McAlexander MA, Herrick CA, Jordt SE (2013) TRPA1 controls inflammation and pruritogen responses in allergic contact dermatitis. FASEB J 27(9):3549–3563
Acknowledgments
This work was supported by MINECO (Grants BFU2012-39092-C02-01 and CONSOLIDER-INGENIO 2010 CSD2008-00005) and by GVA (Grant PROMETEO/2014/011).
Author information
Authors and Affiliations
Corresponding authors
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2016 Springer International Publishing Switzerland
About this chapter
Cite this chapter
Taberner, F.J., Devesa, I., Ferrer-Montiel, A. (2016). Calcium Entry Through Thermosensory Channels. In: Rosado, J. (eds) Calcium Entry Pathways in Non-excitable Cells. Advances in Experimental Medicine and Biology, vol 898. Springer, Cham. https://doi.org/10.1007/978-3-319-26974-0_12
Download citation
DOI: https://doi.org/10.1007/978-3-319-26974-0_12
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-26972-6
Online ISBN: 978-3-319-26974-0
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)