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What Do We Really Know and What Do We Need to Know: Some Controversies, Perspectives, and Surprises

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Mammalian Transient Receptor Potential (TRP) Cation Channels

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 223))

Abstract

TRP channels comprise one of the most rapid growing research topics in ion channel research, in fields related to ion channels including channelopathies and translational medicine. We provide here a critical survey on our current knowledge of TRP channels and highlight some of the still open or controversial questions. This comprises questions related to evolution of TRP channels; biophysics, i.e., permeation; pore properties and gating; modulation; the still-elusive 3D structure; and channel subunits but also their role as general sensory channels and in human diseases. We will conclude that our knowledge on TRP channels is still at the very beginning of an exciting research journey.

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Notes

  1. 1.

    Moyer B, Zlotnik A, Hevezi P, Soto H, Lu M, Gao N, Servant G, Brust P, Williams M, Kalabat D, et al. (2009) Identification of Trpml3 (Mcoln3) as a salty taste receptor and use in assays for identifying taste (salty) modulators and/or therapeutics that modulate sodium transport, absorption or excretion and/or aldosterone and/or vasopressin production or release. SENOMYX patent.

References

  • Almers W (1978) Gating currents and charge movements in excitable membranes. Rev Physiol Biochem Pharmacol 82:96–190

    CAS  PubMed  Google Scholar 

  • Anderson NL, Anderson NG (1998) Proteome and proteomics: new technologies, new concepts, and new words. Electrophoresis 19:1853–1861

    CAS  PubMed  Google Scholar 

  • Anderson L, Seilhamer J (1997) A comparison of selected mRNA and protein abundances in human liver. Electrophoresis 18:533–537

    CAS  PubMed  Google Scholar 

  • Andersson DA, Gentry C, Moss S, Bevan S (2009) Clioquinol and pyrithione activate TRPA1 by increasing intracellular Zn2+. Proc Natl Acad Sci U S A 106:8374–8379

    CAS  PubMed Central  PubMed  Google Scholar 

  • Asai Y, Holt JR, Géléoc GS (2010) A quantitative analysis of the spatiotemporal pattern of transient receptor potential gene expression in the developing mouse cochlea. J Assoc Res Otolaryngol 11:27–37

    PubMed Central  PubMed  Google Scholar 

  • Asakawa M, Yoshioka T, Matsutani T, Hikita I, Suzuki M, Oshima I, Tsukahara K, Arimura A, Horikawa T, Hirasawa T, Sakata T (2006) Association of a mutation in TRPV3 with defective hair growth in rodents. J Invest Dermatol 126:2664–2672

    CAS  PubMed  Google Scholar 

  • Audo I, Kohl S, Leroy BP, Munier FL, Guillonneau X, Mohand-Said S, Bujakowska K, Nandrot EF, Lorenz B, Preising M et al (2009) TRPM1 Is mutated in patients with autosomal-recessive complete congenital stationary night blindness. Am J Hum Genet 85:720–729

    CAS  PubMed Central  PubMed  Google Scholar 

  • Bai CX, Giamarchi A, Rodat-Despoix L, Padilla F, Downs T, Tsiokas L, Delmas P (2008) Formation of a new receptor-operated channel by heteromeric assembly of TRPP2 and TRPC1 subunits. EMBO Rep 9:472–479

    CAS  PubMed Central  PubMed  Google Scholar 

  • Banke TG, Wickenden AD (2009) Intracellular zinc irritates TRPA1. Nat Chem Biol 5:141–142

    CAS  PubMed  Google Scholar 

  • Bavassano C, Marvaldi L, Langeslag M, Sarg B, Lindner H, Klimaschewski L, Kress M, Ferrer-Montiel A, Knaus HG (2013) Identification of voltage-gated K channel beta 2 (Kvbeta2) subunit as a novel interaction partner of the pain transducer Transient Receptor Potential Vanilloid 1 channel (TRPV1). Biochimica et biophysica acta 1833:3166–3175

    CAS  PubMed  Google Scholar 

  • Beck A, Speicher T, Stoerger C, Sell T, Dettmer V, Jusoh SA, Abdulmughni A, Cavali Eacute A, Philipp SE, Zhu MX et al (2013) Conserved gating elements in TRPC4 and TRPC5 channels. J Biol Chem 288:19471–19483

    CAS  PubMed Central  PubMed  Google Scholar 

  • Bellono NW, Oancea E (2013) UV light phototransduction depolarizes human melanocytes. Channels (Austin) 7(3), ahead of pring, PMID 23764911

    Google Scholar 

  • Bellono NW, Kammel LG, Zimmerman AL, Oancea E (2013) UV light phototransduction activates transient receptor potential A1 ion channels in human melanocytes. Proc Natl Acad Sci U S A 110:2383–2388

    CAS  PubMed Central  PubMed  Google Scholar 

  • Benedikt J, Samad A, Ettrich R, Teisinger J, Vlachova V (2009) Essential role for the putative S6 inner pore region in the activation gating of the human TRPA1 channel. Biochim Biophys Acta 1793:1279–1288

    CAS  PubMed  Google Scholar 

  • Berbey C, Weiss N, Legrand C, Allard B (2009) Transient receptor potential canonical type 1 (TRPC1) operates as a sarcoplasmic reticulum calcium leak channel in skeletal muscle. J Biol Chem 284:36387–36394

    CAS  PubMed Central  PubMed  Google Scholar 

  • Birerdinc A, Jarrar M, Stotish T, Randhawa M, Baranova A (2012) Manipulating molecular switches in brown adipocytes and their precursors: a therapeutic potential. Prog Lipid Res 52:51–61

    PubMed  Google Scholar 

  • Bohlen CJ, Priel A, Zhou S, King D, Siemens J, Julius D (2010) A bivalent Tarantula toxin activates the capsaicin receptor, TRPV1, by targeting the outer pore domain. Cell 141:834–845

    CAS  PubMed Central  PubMed  Google Scholar 

  • Bright JN, Sansom MS (2004) Kv channel S6 helix as a molecular switch: simulation studies. IEE Proc Nanobiotechnol 151:17–27

    CAS  PubMed  Google Scholar 

  • Cai X (2008) Unicellular Ca2+ signaling ‘Toolkit’ at the origin of metazoa. Mol Biol Evol 25:1357–1361

    CAS  PubMed  Google Scholar 

  • Cao E, Cordero-Morales JF, Liu B, Qin F, Julius D (2013) TRPV1 channels are intrinsically heat sensitive and negatively regulated by phosphoinositide lipids. Neuron 77:667–679

    CAS  PubMed Central  PubMed  Google Scholar 

  • Cavanaugh EJ, Simkin D, Kim D (2008) Activation of TRPA1 by mustard oil, tetrahydrocannabinol and Ca2+ reveals different functional states of TRPA1. Neuroscience 154:1467–1476

    CAS  PubMed  Google Scholar 

  • Cavanaugh DJ, Chesler AT, Braz JM, Shah NM, Julius D, Basbaum AI (2011a) Restriction of transient receptor potential vanilloid-1 to the peptidergic subset of primary afferent neurons follows its developmental downregulation in nonpeptidergic neurons. J Neurosci 31:10119–10127

    CAS  PubMed Central  PubMed  Google Scholar 

  • Cavanaugh DJ, Chesler AT, Jackson AC, Sigal YM, Yamanaka H, Grant R, O’Donnell D, Nicoll RA, Shah NM, Julius D, Basbaum AI (2011b) Trpv1 reporter mice reveal highly restricted brain distribution and functional expression in arteriolar smooth muscle cells. J Neurosci 31:5067–5077

    CAS  PubMed Central  PubMed  Google Scholar 

  • Chahl LA (2007) TRP’s: links to schizophrenia? Biochim Biophys Acta 1772:968–977

    CAS  PubMed  Google Scholar 

  • Chen J, Zhang XF, Kort ME, Huth JR, Sun C, Miesbauer LJ, Cassar SC, Neelands T, Scott VE, Moreland RB et al (2008) Molecular determinants of species-specific activation or blockade of TRPA1 channels. J Neurosci 28:5063–5071

    CAS  PubMed  Google Scholar 

  • 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

    PubMed Central  PubMed  Google Scholar 

  • Cheng X, Shen D, Samie M, Xu H (2010) Mucolipins: intracellular TRPML1-3 channels. FEBS Lett 584:2013–2021

    CAS  PubMed Central  PubMed  Google Scholar 

  • Cho H, Yang YD, Lee J, Lee B, Kim T, Jang Y, Back SK, Na HS, Harfe BD, Wang F et al (2012) The calcium-activated chloride channel anoctamin 1 acts as a heat sensor in nociceptive neurons. Nat Neurosci 15:1015–1021

    CAS  PubMed  Google Scholar 

  • Chu B, Postma M, Hardie RC (2013) Fractional Ca2+ currents through TRP and TRPL channels in Drosophila photoreceptors. Biophys J 104:1905–1916

    CAS  PubMed Central  PubMed  Google Scholar 

  • Chuang HH, Prescott ED, Kong H, Shields S, Jordt SE, Basbaum AI, Chao MV, Julius D (2001) Bradykinin and nerve growth factor release the capsaicin receptor from PtdIns(4,5)P2-mediated inhibition. Nature 411:957–962

    CAS  PubMed  Google Scholar 

  • Chun JN, Lim JM, Kang Y, Kim EH, Shin YC, Kim HG, Jang D, Kwon D, Shin SY, So I, Jeon JH (2013) A network perspective on unraveling the role of TRP channels in biology and disease. Pflugers Arch 466:173–182

    PubMed  Google Scholar 

  • Chung MK, Guler AD, Caterina MJ (2008) TRPV1 shows dynamic ionic selectivity during agonist stimulation. Nat Neurosci 11:555–564

    CAS  PubMed  Google Scholar 

  • Cook NL, Van Den Heuvel C, Vink R (2009) Are the transient receptor potential melastatin (TRPM) channels important in magnesium homeostasis following traumatic brain injury? Magnes Res 22:225–234

    CAS  PubMed  Google Scholar 

  • Cook NL, Vink R, Helps SC, Manavis J, van den Heuvel C (2010) Transient receptor potential melastatin 2 expression is increased following experimental traumatic brain injury in rats. J Mol Neurosci 42:192–199

    CAS  PubMed  Google Scholar 

  • Cornell RA, Aarts M, Bautista D, Garcia-Anoveros J, Kiselyov K, Liman ER (2008) A double TRPtych: six views of transient receptor potential channels in disease and health. J Neurosci 28:11778–11784

    CAS  PubMed Central  PubMed  Google Scholar 

  • Cosens DJ, Manning A (1969) Abnormal electroretinogram from a Drosophila mutant. Nature 224:285–287

    CAS  PubMed  Google Scholar 

  • Courjaret R, Hubrack S, Daalis A, Dib M, Machaca K (2013) The Xenopus TRPV6 homolog encodes a Mg-permeant channel that is inhibited by interaction with TRPC1. J Cell Physiol 228:2386–2398

    CAS  PubMed  Google Scholar 

  • Cuajungco MP, Grimm C, Oshima K, D’Hoedt D, Nilius B, Mensenkamp AR, Bindels RJ, Plomann M, Heller S (2006) PACSINs bind to the TRPV4 cation channel: PACSIN 3 modulates the subcellular localization of TRPV4. J Biol Chem 281:18753–18762

    CAS  PubMed  Google Scholar 

  • Cvetkov TL, Huynh KW, Cohen MR, Moiseenkova-Bell VY (2011) Molecular architecture and subunit organization of TRPA1 channel revealed by electron microscopy. J Biol Chem 286:38168–38176

    CAS  PubMed Central  PubMed  Google Scholar 

  • D’hoedt D, Owsianik G, Prenen P, Cuajungco MP, Grimm G, Heller S, Voets T, Nilius B (2007) Stimulus-specific modulation of the cation channel TRPV4 by PACSIN 3. J Biol Chem 283:6272–6280

    Google Scholar 

  • Damann N, Voets T, Nilius B (2008) TRPs in our senses. Curr Biol 18:R880–889

    CAS  PubMed  Google Scholar 

  • de la Roche J, Eberhardt MJ, Klinger AB, Stanslowksy N, Wegner F, Koppert W, Reeh PW, Lampert A, Fischer MJ, Leffler A (2013) The molecular basis for species-specific activation of human TRPA1 by protons involves poorly conserved residues within transmembrane domains 5 and 6. J Biol Chem 288:20280–20292

    PubMed  Google Scholar 

  • Demion M, Bois P, Launay P, Guinamard R (2007) TRPM4, a Ca(2+)-activated nonselective cation channel in mouse sino-atrial node cells. Cardiovasc Res 73:531–538

    CAS  PubMed  Google Scholar 

  • den Dekker E, Schoeber J, Topala CN, van de Graaf SF, Hoenderop JG, Bindels RJ (2005) Characterization of a Madin-Darby canine kidney cell line stably expressing TRPV5. Pflugers Arch 450:236–244

    Google Scholar 

  • Devi S, Kedlaya R, Maddodi N, Bhat KM, Weber CS, Valdivia HH, Setaluri V (2009) Calcium homeostasis in human melanocytes: role of transient receptor potential melastatin 1 (TRPM1) and its regulation by ultraviolet light. Am J Physiol Cell Physiol 297:C679–C687

    CAS  PubMed Central  PubMed  Google Scholar 

  • Dhaka A, Viswanath V, Patapoutian A (2006) TRP ion channels and temperature sensation. Annu Rev Neurosci 29:135–161

    CAS  PubMed  Google Scholar 

  • Dong XP, Shen D, Wang X, Dawson T, Li X, Zhang Q, Cheng X, Zhang Y, Weisman LS, Delling M, Xu H (2010) PI(3,5)P(2) controls membrane traffic by direct activation of mucolipin Ca release channels in the endolysosome. Nat Commun 1:38

    PubMed Central  PubMed  Google Scholar 

  • Dong HW, Davis JC, Ding SY, Nai Q, Zhou FM, Ennis M (2012) Expression of transient receptor potential (TRP) channel mRNAs in the mouse olfactory bulb. Neurosci Lett 524:49–54

    CAS  PubMed  Google Scholar 

  • Earley S, Pauy T, Drapp R, Tavares MJ, Liedtke W, Brayden JE (2009) TRPV4-dependent dilation of peripheral resistance arteries influences arterial pressure. Am J Physiol 297:H1096–H1102

    CAS  Google Scholar 

  • Ebert J, Westhoff G (2006) Behavioural examination of the infrared sensitivity of rattlesnakes (Crotalus atrox). J Comp Physiol A 192:941–947

    CAS  Google Scholar 

  • Eijkelkamp N, Quick K, Wood JN (2013) Transient receptor potential channels and mechanosensation. Annu Rev Neurosci 36:519–546

    CAS  PubMed  Google Scholar 

  • Everaerts W, Nilius B, Owsianik G (2010) The vanilloid transient receptor potential channel Trpv4: From structure to disease. Prog Biophys Mol Biol 103:2–17

    CAS  PubMed  Google Scholar 

  • Fecher-Trost C, Wissenbach U, Beck A, Schalkowsky P, Stoerger C, Doerr J, Dembek A, Simon-Thomas M, Weber A, Wollenberg P et al (2013) The in vivo TRPV6 protein starts at a non-AUG triplet decoded as methionine upstream the canonical initiation at AUG. J Biol Chem 288:16629–16644

    CAS  PubMed Central  PubMed  Google Scholar 

  • Feng S, Li H, Tai Y, Huang J, Su Y, Abramowitz J, Zhu MX, Birnbaumer L, Wang Y (2013) Canonical transient receptor potential 3 channels regulate mitochondrial calcium uptake. Proc Natl Acad Sci U S A 110:11011–11016

    CAS  PubMed Central  PubMed  Google Scholar 

  • Fernandes AM, Fero K, Arrenberg AB, Bergeron SA, Driever W, Burgess HA (2012) Deep brain photoreceptors control light-seeking behavior in zebrafish larvae. Curr Biol 22:2042–2047

    CAS  PubMed Central  PubMed  Google Scholar 

  • Fernandes AM, Fero K, Driever W, Burgess HA (2013) Enlightening the brain: linking deep brain photoreception with behavior and physiology. BioEssays 35:775–779

    CAS  PubMed  Google Scholar 

  • Ferrer-Montiel A, Fernández-Carvajal A, Planells-Cases R, Fernández-Ballester G, González-Ros JM, Messeguer A, González-Muñiz R (2012) Advances in modulating thermosensory TRP channels. Expert Opin Ther Pat 22:999–1017

    CAS  PubMed  Google Scholar 

  • Filosa JA, Yao X, Rath G (2013) TRPV4 and the regulation of vascular tone. J Cardiovasc Pharmacol 61:113–119

    CAS  PubMed Central  PubMed  Google Scholar 

  • Flockerzi V, Jung C, Aberle T, Meissner M, Freichel M, Philipp SE, Nastainczyk W, Maurer P, Zimmermann R (2005) Specific detection and semi-quantitative analysis of TRPC4 protein expression by antibodies. Pflugers Arch 451:81–86

    CAS  PubMed  Google Scholar 

  • Fujiwara Y, Minor DL Jr (2008) X-ray crystal structure of a TRPM assembly domain reveals an antiparallel four-stranded coiled-coil. J Mol Biol 383:854–870

    CAS  PubMed Central  PubMed  Google Scholar 

  • Fujiwara Y, Kurokawa T, Takeshita K, Kobayashi M, Okochi Y, Nakagawa A, Okamura Y (2012) The cytoplasmic coiled-coil mediates cooperative gating temperature sensitivity in the voltage-gated H(+) channel Hv1. Nat Commun 3:816

    PubMed  Google Scholar 

  • Gamal El-Din TM, Heldstab H, Lehmann C, Greeff NG (2011) Double gaps along Shaker S4 demonstrate omega currents at three different closed states. Channels (Austin) 4:93–100

    Google Scholar 

  • Garami A, Shimansky YP, Pakai E, Oliveira DL, Gavva NR, Romanovsky AA (2010) Contributions of different modes of TRPV1 activation to TRPV1 antagonist-induced hyperthermia. J Neurosci 30:1435–1440

    CAS  PubMed Central  PubMed  Google Scholar 

  • Garami A, Pakai E, Oliveira DL, Steiner AA, Wanner SP, Almeida MC, Lesnikov VA, Gavva NR, Romanovsky AA (2011) Thermoregulatory phenotype of the Trpv1 knockout mouse: thermoeffector dysbalance with hyperkinesis. J Neurosci 31:721–173

    Google Scholar 

  • 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 24:5307–5314

    CAS  PubMed  Google Scholar 

  • Gaudet R (2008a) A primer on ankyrin repeat function in TRP channels and beyond. Mol Biosyst 4:372–379

    CAS  PubMed Central  PubMed  Google Scholar 

  • Gaudet R (2008b) TRP channels entering the structural era. J Physiol 586:3565–3575

    CAS  PubMed Central  PubMed  Google Scholar 

  • Gees M, Colsoul B, Nilius B (2010) The role of transient receptor potential cation channels in Ca2+ signaling. Cold Spring Harb Perspect Biol 2:a003962

    CAS  PubMed Central  PubMed  Google Scholar 

  • Geng J, Liang D, Jiang K, Zhang P (2012) Molecular evolution of the infrared sensory gene TRPA1 in snakes and implications for functional studies. PLoS One 6:e28644

    Google Scholar 

  • Gerzanich V, Woo KS, Vennekens R, Orest Tsymbalyuk SO, Ivanova S, Ivanov A, Geng Z, Chen Z, Nilius B, Flockerzi V et al (2009) De novo expression of TRPM4 initiates secondary hemorrhage in spinal cord injury. Nat Med 15:185–191

    CAS  PubMed Central  PubMed  Google Scholar 

  • Gilliam JC, Wense TG (2011) TRP channel gene expression in the mouse retina. Vision Research 51, 2440-2452.x. Vision Res 51:2440–2452

    CAS  PubMed Central  PubMed  Google Scholar 

  • Gordon-Shaag A, Zagotta WN, Gordon SE (2008) Mechanism of Ca2+-dependent desensitization of TRP channels. Channels 2:125–129

    PubMed  Google Scholar 

  • 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 464:1006–1012

    CAS  PubMed Central  PubMed  Google Scholar 

  • 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 476:88–91

    CAS  PubMed Central  PubMed  Google Scholar 

  • Griffith TN, Varela-Nallar L, Dinamarca MC, Inestrosa NC (2010) Neurobiological effects of hyperforin and its potential in Alzheimer’s disease therapy. Curr Med Chem 17:391–406

    CAS  PubMed  Google Scholar 

  • Gu Q, Lin RL (2010) Heavy metals zinc, cadmium and copper stimulate pulmonary sensory neurons via direct activation of TRPA1. J Appl Physiol 108:891–897

    CAS  PubMed Central  PubMed  Google Scholar 

  • Gygi SP, Rochon Y, Franza BR, Aebersold R (1999) Correlation between protein and mRNA abundance in yeast. Mol Cell Biol 19:1720–1730

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hara K, Kokubo Y, Ishiura H, Fukuda Y, Miyashita A, Kuwano R, Sasaki R, Goto J, Nishizawa M, Kuzuhara S, Tsuji S (2010) TRPM7 is not associated with amyotrophic lateral sclerosis-parkinsonism dementia complex in the Kii peninsula of Japan. Am J Med Genet B Neuropsychiatr Genet 153B:310–313

    CAS  PubMed  Google Scholar 

  • Hardie RC, Franze K (2012) Photomechanical responses in Drosophila photoreceptors. Science 338:260–263

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Hardie RC, Minke B (1993) Novel Ca2+ channels underlying transduction in Drosophila photoreceptors: implications for phosphoinositide-mediated Ca2+ mobilization. Trends Neurosci 16:371–376

    CAS  PubMed  Google Scholar 

  • Hardie RC, Postma M (2008) Phototransduction in microvillar photoreceptors of Drosophila and other invertebrates. In: Basbaum AI, Shepherd GM, Westheimer G (eds) The senses: a comprehensive reference, Vision I. Academic, San Diego, pp 77–130

    Google Scholar 

  • Hermosura MC, Garruto RM (2007) TRPM7 and TRPM2-CANDIDATE susceptibility genes for Western Pacific ALS and PD? Biochim Biophys Acta 1772:822–835

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hermosura MC, Monteilh-Zoller MK, Scharenberg AM, Penner R, Fleig A (2002) Dissociation of the store-operated calcium current ICRAC and the Mg-nucleotide-regulated metal ion current MagNuM. J Physiol (Lond) 539:445–458

    CAS  Google Scholar 

  • Hermosura MC, Nayakanti H, Dorovkov MV, Calderon FR, Ryazanov AG, Haymer DS, Garruto RM (2005) A TRPM7 variant shows altered sensitivity to magnesium that may contribute to the pathogenesis of two Guamanian neurodegenerative disorders. Proc Natl Acad Sci U S A 102:11510–11515

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hermosura M, Cui AM, Go G, Davenport B, Shetler C, Heizer J, Schmitz C, Mocz G, Garruto R, Perraud A-L (2008) Altered functional properties of a TRPM2 variant in Guamanian ALS and PD. Proc Natl Acad Sci U S A 105:18029–18034

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hoenderop JG, Voets T, Hoefs S, Weidema F, Prenen J, Nilius B, Bindels RJ (2003) Homo- and heterotetrameric architecture of the epithelial Ca2+ channels TRPV5 and TRPV6. EMBO J 22:776–785

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hofmann T, Schaefer M, Schultz G, Gudermann T (2002) Subunit composition of mammalian transient receptor potential channels in living cells. Proc Natl Acad Sci U S A 99:7461–7466

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hofmann F, Flockerz IV, Kahl S, Wegener JW (2014) L-type CaV1.2 calcium channels: from in vitro findings to in vivo function. Physiol Rev 94:303–26

    CAS  PubMed  Google Scholar 

  • Hu G, Oboukhova EA, Kumar S, Sturek M, Obukhov AG (2009a) Canonical transient receptor potential channels expression is elevated in a porcine model of metabolic syndrome. Mol Endocrinol 23:689–699

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hu H, Bandell M, Petrus MJ, Zhu MX, Patapoutian A (2009b) Zinc activates damage-sensing TRPA1 ion channels. Nat Chem Biol 5:183–190

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hughes S, Pothecary CA, Jagannath A, Foster RG, Hankins MW, Peirson SN (2012) Profound defects in pupillary responses to light in TRPM-channel null mice: a role for TRPM channels in non-image-forming photoreception. Eur J Neurosci 35:34–43

    PubMed  Google Scholar 

  • Ihara M, Hamamoto S, Miyanoiri Y, Takeda M, Kainosho M, Yabe I, Uozumi N, Yamashita A (2013) Molecular bases of multimodal regulation of a fungal transient receptor potential (TRP) channel. J Biol Chem 288

    Google Scholar 

  • Inada H, Procko E, Sotomayor M, Gaudet R (2012) Structural and biochemical consequences of disease-causing mutations in the ankyrin repeat domain of the human TRPV4 channel. Biochemistry 51:6195–6206

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ito N, Ruegg UT, Kudo A, Miyagoe-Suzuki Y, Takeda S (2012) Activation of calcium signaling through Trpv1 by nNOS and peroxynitrite as a key trigger of skeletal muscle hypertrophy. Nat Med 19:101–106

    PubMed  Google Scholar 

  • Jansson ET, Trkulja CL, Ahemaiti A, Millingen M, Jeffries GD, Jardemark K, Orwar O (2013) Effect of cholesterol depletion on the pore dilation of TRPV1. Mol Pain 9:1

    CAS  PubMed Central  PubMed  Google Scholar 

  • Jeon JP, Lee KP, Park EJ, Sung TS, Kim BJ, Jeon JH, So I (2008) The specific activation of TRPC4 by Gi protein subtype. Biochem Biophys Res Commun 377:538–543

    CAS  PubMed  Google Scholar 

  • Jeon JP, Hong C, Park EJ, Jeon JH, Cho NH, Kim IG, Choe H, Muallem S, Kim HJ, So I (2012) Selective Galphai subunits as novel direct activators of TRPC4 and TRPC5 channels. J Biol Chem 287:17029–17039

    CAS  PubMed Central  PubMed  Google Scholar 

  • Jeon JP, Roh SE, Wie J, Kim J, Kim H, Lee KP, Yang D, Jeon JH, Cho NH, Kim IG et al (2013) Activation of TRPC4beta by Galpha subunit increases Ca selectivity and controls neurite morphogenesis in cultured hippocampal neuron. Cell Calcium 54:307–319

    CAS  PubMed  Google Scholar 

  • Jin X, Touhey J, Gaudet R (2006) Structure of the N-terminal ankyrin repeat domain of the TRPV2 ion channel. J Biol Chem 281:25006–25010

    CAS  PubMed  Google Scholar 

  • Jordt SE, Julius D (2002) Molecular basis for species-specific sensitivity to “hot” chili peppers. Cell 108:421–430

    CAS  PubMed  Google Scholar 

  • Jurkat-Rott K, Holzherr B, Fauler M, Lehmann-Horn F (2010) Sodium channelopathies of skeletal muscle result from gain or loss of function. Pflugers Archiv 460:239–248

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kalia J, Swartz KJ (2013) Exploring structure-function relationships between TRP and Kv channels. Sci Rep 3:1523

    PubMed Central  PubMed  Google Scholar 

  • Karashima Y, Prenen J, Meseguer V, Owsianik G, Voets T, Nilius B (2008) Modulation of the transient receptor potential channel TRPA1 by phosphatidylinositol 4,5-biphosphate manipulators. Pflugers Arch 457:77–89

    CAS  PubMed  Google Scholar 

  • Karashima Y, Prenen J, Talavera K, Janssens A, Voets T, Nilius B (2010) Agonist-induced changes in Ca(2+) permeation through the nociceptor cation channel TRPA1. Biophys J 98:773–783

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kassmann M, Harteneck C, Zhu Z, Nurnberg B, Tepel M, Gollasch M (2013) TRPV1, TRPV4, and the kidney. Acta Physiol (Oxf) 207:546–564

    CAS  Google Scholar 

  • Kedei N, Szabo T, Lile JD, Treanor JJ, Olah Z, Iadarola MJ, Blumberg PM (2001) Analysis of the native quaternary structure of vanilloid receptor 1. J Biol Chem 276:28613–28619

    CAS  PubMed  Google Scholar 

  • Kim D, Cavanaugh EJ (2007) Requirement of a soluble intracellular factor for activation of transient receptor potential A1 by pungent chemicals: role of inorganic polyphosphates. J Neurosci 27:6500–6509

    CAS  PubMed  Google Scholar 

  • Kim AY, Tang Z, Liu Q, Patel KN, Maag D, Geng Y, Dong X (2008) Pirt, a phosphoinositide-binding protein, functions as a regulatory subunit of TRPV1. Cell 133:475–485

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kim D, Cavanaugh E, Simkin D (2009) Inhibition of transient receptor potential A1 by phosphatidylinositol-4,5-bisphosphate. Am J Physiol Cell Physiol 295:C92–99

    Google Scholar 

  • Kirkwood NK, Albert JT (2013) Sensory transduction: confusing the senses. Curr Biol 23:R22–23

    CAS  PubMed  Google Scholar 

  • Kiselyov K, Soyombo A, Muallem S (2007) TRPpathias. J Physiol 578:641–653

    CAS  PubMed Central  PubMed  Google Scholar 

  • Klein RM, Ufret-Vincenty CA, Hua L, Gordon SE (2008) Determinants of molecular specificity in phosphoinositide regulation: PI(4,5)P2 is the endogenous lipid regulating TRPV1. J Biol Chem 283:26208–26216

    CAS  PubMed Central  PubMed  Google Scholar 

  • Klionsky L, Tamir R, Gao B, Wang W, Immke DC, Nishimura N, Gavva NR (2007) Species-specific pharmacology of Trichloro(sulfanyl)ethyl benzamides as transient receptor potential ankyrin 1 (TRPA1) antagonists. Mol Pain 3:39

    PubMed Central  PubMed  Google Scholar 

  • Kohler R, Heyken WT, Heinau P, Schubert R, Si H, Kacik M, Busch C, Grgic I, Maier T, Hoyer J (2006) Evidence for a functional role of endothelial transient receptor potential V4 in shear stress-induced vasodilatation. Arterioscler Thromb Vasc Biol 26:1495–1502

    PubMed  Google Scholar 

  • Koike C, Obara T, Uriu Y, Numata T, Sanuki R, Miyata K, Koyasu T, Ueno S, Funabiki K, Tani A et al (2010) TRPM1 is a component of the retinal ON bipolar cell transduction channel in the mGluR6 cascade. Proc Natl Acad Sci U S A 107:332–337

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kremeyer B, Lopera F, Cox JJ, Momin A, Rugiero F, Marsh S, Woods CG, Jones NG, Paterson KJ, Fricker FR et al (2010) A gain-of-function mutation in TRPA1 causes familial episodic pain syndrome. Neuron 66:671–680

    CAS  PubMed  Google Scholar 

  • Landman N, Jeong SY, Shin SY, Voronov SV, Serban G, Kang MS, Park MK, Di Paolo G, Chung S, Kim T-W (2006) Presenilin mutations linked to familial Alzheimer’s disease cause an imbalance in phosphatidylinositol 4,5-bisphosphate metabolism. Proc Natl Acad Sci U S A 103:19524–19529

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lee JH, Lee Y, Ryu H, Kang DW, Lee J, Lazar J, Pearce LV, Pavlyukovets VA, Blumberg PM, Choi S (2011) Structural insights into transient receptor potential vanilloid type 1 (TRPV1) from homology modeling, flexible docking, and mutational studies. J Comput Aided Mol Des 25:317–327

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lepichon JB, Bittel DC, Graf WD, Yu S (2010) A 15q13.3 homozygous microdeletion associated with a severe neurodevelopmental disorder suggests putative functions of the TRPM1, CHRNA7, and other homozygously deleted genes. Am J Med Genet A 152A:1300–1304

    CAS  PubMed  Google Scholar 

  • Leuner K, Kazanski V, Muller M, Essin K, Henke B, Gollasch M, Harteneck C, Muller WE (2007) Hyperforin-a key constituent of St. John’s wort specifically activates TRPC6 channels. FASEB J 21:4101–4111

    CAS  PubMed  Google Scholar 

  • Leuner K, Heiser JH, Derksen S, Mladenov MI, Fehske CJ, Schubert R, Gollasch M, Schneider G, Harteneck C, Chatterjee SS, Muller WE (2010) Simple 2,4 diacylphloroglucinols as TRPC6 activators - identification of a novel pharmacophore. Mol Pharmacol 77:368–377

    CAS  PubMed  Google Scholar 

  • Li L, Chen J, Ni Y, Feng X, Zhao Z, Wang P, Sun J, Yu H, Yan Z, Liu D et al (2012) TRPV1 activation prevents nonalcoholic fatty liver through UCP2 upregulation in mice. Pflugers Archiv 463:727–732

    CAS  PubMed  Google Scholar 

  • Li Q, Li L, Wang F, Chen J, Zhao Y, Wang P, Nilius B, Liu D, Zhu Z (2013) Dietary capsaicin prevents nonalcoholic fatty liver disease through transient receptor potential vanilloid 1-mediated peroxisome proliferator-activated receptor delta activation. Pflugers Archiv 465:1303–1316

    CAS  PubMed  Google Scholar 

  • Liao Y, Erxleben C, Abramowitz J, Flockerzi V, Zhu MX, Armstrong DL, Birnbaumer L (2008) Functional interactions among Orai1, TRPCs, and STIM1 suggest a STIM-regulated heteromeric Orai/TRPC model for SOCE/Icrac channels. Proc Natl Acad Sci U S A 105:2895–2900

    CAS  PubMed Central  PubMed  Google Scholar 

  • Liscombe DK, Facchini PJ (2008) Evolutionary and cellular webs in benzylisoquinoline alkaloid biosynthesis. Curr Opin Biotechnol 19:173–180

    CAS  PubMed  Google Scholar 

  • Lishko PV, Procko E, Jin X, Phelps CB, Gaudet R (2007) The Ankyrin repeats of TRPV1 bind multiple ligands and modulate channel sensitivity. Neuron 54:905–918

    CAS  PubMed  Google Scholar 

  • Liu D, Zhu Z, Tepel M (2008) The role of transient receptor potential channels in metabolic syndrome. Hypertens Res 31:1989–1995

    CAS  PubMed  Google Scholar 

  • Long SB, Campbell EB, Mackinnon R (2005) Crystal structure of a mammalian voltage-dependent Shaker family K+ channel. Science 309:897–903

    CAS  PubMed  Google Scholar 

  • Loot AE, Popp R, Fisslthaler B, Vriens J, Nilius B, Fleming I (2008) Role of cytochrome P450-dependent TRPV4 activation in flow-induced vasodilatation. Cardiovasc Res 80:445–452

    CAS  PubMed  Google Scholar 

  • Lucas RJ (2013) Mammalian inner retinal photoreception. Curr Biol 23:R125–133

    CAS  PubMed  Google Scholar 

  • Lukacs V, Yudin Y, Hammond GR, Sharma E, Fukami K, Rohacs T (2013) Distinctive changes in plasma membrane phosphoinositides underlie differential regulation of TRPV1 in nociceptive neurons. J Neurosci 33:11451–11463

    CAS  PubMed Central  PubMed  Google Scholar 

  • Luo Z, Ma L, Zhao Z, He H, Yang D, Feng X, Ma S, Chen X, Zhu T, Cao T et al (2012) TRPV1 activation improves exercise endurance and energy metabolism through PGC-1alpha upregulation in mice. Cell Res 22:551–564

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ma X, Qiu S, Luo J, Ma Y, Ngai CY, Shen B, Wong CO, Huang Y, Yao X (2010) Functional role of TRPV4-TRPC1 complex in flow-induced Ca2+ influx. Arterioscler Thromb Vasc Biol 30:851–858

    CAS  PubMed  Google Scholar 

  • Ma X, Nilius B, Wong JW, Huang Y, Yao X (2011) Electrophysiological properties of heteromeric TRPV4-C1 channels. Biochim Biophys Acta 1808:2807–2818

    Google Scholar 

  • Madrid R, de la Pen E, Donovan-Rodriguez T, Belmonte C, Viana F (2009) Variable threshold of trigeminal cold-thermosensitive neurons is determined by a balance between TRPM8 and Kv1 potassium channels. J Physiol (Lond) 587:1961–1976

    Google Scholar 

  • Matsuura H, Sokabe T, Kohno K, Tominaga M, Kadowaki T (2009) Evolutionary conservation and changes in insect TRP channels. BMC Evol Biol 9:228

    PubMed Central  PubMed  Google Scholar 

  • McNulty S, Fonfria E (2005) The role of TRPM channels in cell death. Pflügers Arch 451:235–242

    CAS  PubMed  Google Scholar 

  • Meissner M, Obmann VC, Hoschke M, Link S, Jung M, Held G, Philipp SE, Zimmermann R, Flockerzi V (2011) Lessons of studying TRP channels with antibodies. In: Zhu MX (ed) TRP channels. CRC Press, Boca Raton, FL, pp 135–148

    Google Scholar 

  • 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 105:7451–7455

    CAS  PubMed Central  PubMed  Google Scholar 

  • Molnar T, Barabas P, Birnbaumer L, Punzo C, Kefalov V, Krizaj D (2012) Store-operated channels regulate intracellular calcium in mammalian rods. J Physiol 590:3465–3481

    CAS  PubMed Central  PubMed  Google Scholar 

  • Montell C (2012) Drosophila visual transduction. Trends Neurosci 35:356–363

    CAS  PubMed Central  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Montell C, Birnbaumer L, Flockerzi V, Bindels RJ, Bruford EA, Caterina MJ, Clapham D, Harteneck C, Heller S, Julius D et al (2002) A unified nomenclature for the superfamily of TRP cation channels. Mol Cell 9:229–231

    CAS  PubMed  Google Scholar 

  • Moore C, Cevikbas F, Pasolli HA, Chen Y, Kong W, Kempkes C, Parekh P, Lee SH, Kontchoua N-A, Ye I et al (2013) UVB radiation generates sunburn pain and affects skin by activating epidermal TRPV4 ion channels and triggering endothelin-1 signaling. Proc Natl Acad Sci U S A 110:E3225–3234

    CAS  PubMed Central  PubMed  Google Scholar 

  • Morgans CW, Zhang J, Jeffrey BG, Nelson SM, Burke NS, Duvoisin RM, Brown RL (2009) TRPM1 is required for the depolarizing light response in retinal ON-bipolar cells. Proc Natl Acad Sci U S A 106:19174–19178

    CAS  PubMed Central  PubMed  Google Scholar 

  • Mori Y, Wakamori M, Miyakawa T, Hermosura M, Hara Y, Nishida M, Hirose K, Mizushima A, Kurosaki M, Mori E et al (2002) Transient receptor potential 1 regulates capacitative Ca(2+) entry and Ca(2+) release from endoplasmic reticulum in B lymphocytes. J Exp Med 195:673–681

    CAS  PubMed Central  PubMed  Google Scholar 

  • Moussaieff A, Mechoulam R (2009) Boswellia resin: from religious ceremonies to medical uses; a review of in-vitro, in-vivo and clinical trials. J Pharm Pharmacol 61:1281–1293

    CAS  PubMed  Google Scholar 

  • Moussaieff A, Rimmerman N, Bregman T, Straiker A, Felder CC, Shoham S, Kashman Y, Huang SM, Lee H, Shohami E et al (2008) Incensole acetate, an incense component, elicits psychoactivity by activating TRPV3 channels in the brain. FASEB J 22:3024–3034

    CAS  PubMed Central  PubMed  Google Scholar 

  • Muller CS, Haupt A, Bildl W, Schindler J, Knaus HG, Meissner M, Rammner B, Striessnig J, Flockerzi V, Fakler B, Schulte U (2010) Quantitative proteomics of the Cav2 channel nano-environments in the mammalian brain. Proc Natl Acad Sci U S A 107:14950–14957

    PubMed Central  PubMed  Google Scholar 

  • Nagatomo K, Ishii H, Yamamoto T, Nakajo K, Kubo Y (2010) The Met268Pro mutation of mouse TRPA1 changes the effect of caffeine from activation to suppression. Biophys J 99:3609–3618

    CAS  PubMed Central  PubMed  Google Scholar 

  • Nakamura M, Sanuki R, Yasuma TR, Onishi A, Nishiguchi KM, Koike C, Kadowaki M, Kondo M, Miyake Y, Furukawa T (2010) TRPM1 mutations are associated with the complete form of congenital stationary night blindness. Mol Vis 16:425–437

    CAS  PubMed Central  PubMed  Google Scholar 

  • Nieto-Posadas A, Jara-Oseguera A, Rosenbaum T (2011) TRP channel gating physiology. Curr Top Med Chem 11:2131–2150

    CAS  PubMed  Google Scholar 

  • Nilius B (2007) TRP channels in disease. Biochim Biophys Acta 1772:805–812

    CAS  PubMed  Google Scholar 

  • Nilius B, Appendino G (2011) Tasty and healthy TR(i)PS: the human quest for culinary pungency. EMBO Rep 12:1094–1101

    CAS  PubMed Central  PubMed  Google Scholar 

  • Nilius B, Appendino G (2013) Spices: the savory and beneficial science of pungency. Rev Physiol Biochem Pharmacol 164:1–76

    PubMed  Google Scholar 

  • Nilius B, Honore E (2013) Sensing pressure with ion channels. Trends Neurosci 35:477–486

    Google Scholar 

  • Nilius B, Owsianik G (2010a) Channelopathies converge on TRPV4. Nat Genet 42:98–100

    CAS  PubMed  Google Scholar 

  • Nilius B, Owsianik G (2010b) Transient receptor potential channelopathies. Pflugers Archiv 460:437–450

    CAS  PubMed  Google Scholar 

  • Nilius B, Owsianik G (2011) The transient receptor potential family of ion channels. Genome Biol 12:218–229

    CAS  PubMed Central  PubMed  Google Scholar 

  • Nilius B, Voets T (2013) The puzzle of TRPV4 channelopathies. EMBO Rep 14:152–163

    CAS  PubMed Central  PubMed  Google Scholar 

  • Nilius B, Vennekens R, Prenen J, Hoenderop JG, Bindels RJ, Droogmans G (2000) Whole-cell and single channel monovalent cation currents through the novel rabbit epithelial Ca2+ channel ECaC. J Physiol (London) 527:239–248

    CAS  Google Scholar 

  • Nilius B, Prenen J, Tang J, Wang C, Owsianik G, Janssens A, Voets T, Zhu MX (2005a) Regulation of the Ca2+ sensitivity of the nonselective cation channel TRPM4. J Biol Chem 280:6423–6433

    CAS  PubMed  Google Scholar 

  • Nilius B, Talavera K, Owsianik G, Prenen J, Droogmans G, Voets T (2005b) Gating of TRP channels: a voltage connection? J Physiol (Lond) 567:33–44

    CAS  Google Scholar 

  • 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 25:467–478

    CAS  PubMed Central  PubMed  Google Scholar 

  • Nilius B, Owsianik G, Voets T, Peters JA (2007) Transient receptor potential channels in disease. Physiol Rev 87:165–217

    CAS  PubMed  Google Scholar 

  • Nilius B, Owsianik G, Voets T (2008) Transient receptor potential channels meet phosphoinositides. EMBO J 27:2809–2816

    CAS  PubMed Central  PubMed  Google Scholar 

  • Nilius B, Prenen J, Owsianik G (2011) Irritating channels: the case of TRPA1. J Physiol 589:1543–1549

    CAS  PubMed Central  PubMed  Google Scholar 

  • Nilius B, Appendino G, Owsianik G (2012) The transient receptor potential channel TRPA1: from gene to pathophysiology. Pflugers Archiv 464:425–458

    CAS  PubMed  Google Scholar 

  • Nilius B, Biro T, Owsianik G (2014) TRPV3: time to decipher a poorly understood family member! J Physiol 592:295–304

    CAS  PubMed  Google Scholar 

  • Ong HL, Chen J, Chataway T, Brereton H, Zhang L, Downs T, Tsiokas L, Barritt G (2002) Specific detection of the endogenous transient receptor potential (TRP)-1 protein in liver and airway smooth muscle cells using immunoprecipitation and Western-blot analysis. Biochem J 364:641–648

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ong EC, Nesin V, Long CL, Bai CX, Guz JL, Ivanov IP, Abramowitz J, Birnbaumer L, Humphrey MB, Tsiokas L (2013) A TRPC1-dependent pathway regulates osteoclast formation and function. J Biol Chem 288:22219–22232

    CAS  PubMed  Google Scholar 

  • Orio P, Parra A, Madrid R, Gonzalez O, Belmonte C, Viana F (2013) Role of Ih in the firing pattern of mammalian cold thermoreceptor endings. J Neurophysiol 108:3009–3023

    Google Scholar 

  • Otsuguro KI, Tang J, Tang Y, Xiao R, Freichel M, Tsvilovskyy V, Ito S, Flockerzi V, Zhu MX, Zholos AV (2008) Isoform-specific inhibition of TRPC4 channel by phosphatidylinositol 4,5-bisphosphate. J Biol Chem 283:10026–10036

    CAS  PubMed Central  PubMed  Google Scholar 

  • Owsianik G, Talavera K, Voets T, Nilius B (2006) Permeation and selectivity of trp channels. Annu Rev Physiol 68:685–717

    CAS  PubMed  Google Scholar 

  • Pan B, Géléoc GS, Asai Y, Horwitz GC, Kurima K, Ishikawa K, Kawashima Y, Griffith AJ, Holt JR (2013) TMC1 and TMC2 are components of the mechanotransduction channel in hair cells of the mammalian inner ear. Neuron 79:504–515

    CAS  PubMed  Google Scholar 

  • Panzano VC, Kang K, Garrity PA (2010) Infrared snake eyes: TRPA1 and the thermal sensitivity of the snake pit organ. Sci Signal 3:22

    Google Scholar 

  • Papakosta M, Dalle C, Haythornthwaite A, Cao L, Stevens EB, Burgess G, Russell R, Cox PJ, Phillips SC, Grimm C (2011) Chimeric approach reveals that differences in the TRPV1 pore domain determine species-specific sensitivity to block of heat activation. J Biol Chem 286:39663–33967

    CAS  PubMed Central  PubMed  Google Scholar 

  • Patapoutian A, Peier AM, Story GM, Viswanath V (2003) ThermoTRP channels and beyond: mechanisms of temperature sensation. Nat Rev Neurosci 4:529–539

    CAS  PubMed  Google Scholar 

  • Phelps CB, Procko E, Lishko PV, Wang RR, Gaudet R (2007) Insights into the roles of conserved and divergent residues in the ankyrin repeats of TRPV ion channels. Channels (Austin) 1:148–151

    Google Scholar 

  • 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 47:2476–2484

    CAS  PubMed Central  PubMed  Google Scholar 

  • 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 285:731–740

    CAS  PubMed Central  PubMed  Google Scholar 

  • Pickard GE, Sollars PJ (2012) Intrinsically photosensitive retinal ganglion cells. Rev Physiol Biochem Pharmacol 162:59–90

    CAS  PubMed  Google Scholar 

  • Pradet-Balade B, Boulme F, Beug H, Mullner EW, Garcia-Sanz JA (2001) Translation control: bridging the gap between genomics and proteomics? Trends Biochem Sci 26:225–229

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Prole DL, Taylor CW (2011) Identification of intracellular and plasma membrane calcium channel homologues in pathogenic parasites. PLoS One 6:e26218

    CAS  PubMed Central  PubMed  Google Scholar 

  • Prole DL, Taylor CW (2012) Identification and analysis of cation channel homologues in human pathogenic fungi. PLoS One 7:e42404

    CAS  PubMed Central  PubMed  Google Scholar 

  • Prütting S, Grissmer S (2011) A novel current pathway parallel to the central pore in a mutant voltage-gated potassium channel. J Biol Chem 286:20031–20042

    PubMed Central  PubMed  Google Scholar 

  • Ramsey IS, Delling M, Clapham DE (2006) An introduction to TRP channels. Annu Rev Physiol 68:619–647

    CAS  PubMed  Google Scholar 

  • Rath G, Dessy C, Feron O (2009) Caveolae, caveolin and control of vascular tone: nitric oxide (NO) and endothelium derived hyperpolarizing factor (EDHF) regulation. J Physiol Pharmacol 60(Suppl 4):105–109

    PubMed  Google Scholar 

  • Rempe DA, Takano T, Nedergaard M (2009) TR(I)Pping towards treatment for ischemia. Nat Neurosci 12:1215–1216

    CAS  PubMed  Google Scholar 

  • Richards MW, Butcher AJ, Dolphin AC (2004) Ca2+ channel beta-subunits: structural insights AID our understanding. Trends Pharmacol Sci 25:626–632

    CAS  PubMed  Google Scholar 

  • Rohacs T (2013) Regulation of transient receptor potential channels by the phospholipase C pathway. Adv Biol Regul 53:341–355

    CAS  PubMed  Google Scholar 

  • Rohacs T, Nilius B (2007) Regulation of transient receptor potential (trp) channels by phosphoinositides. Pflugers Archiv 455:157–168

    CAS  PubMed  Google Scholar 

  • Ryu S, Liu B, Yao J, Fu Q, Qin F (2007) Uncoupling proton activation of vanilloid receptor TRPV1. J Neurosci 27:12797–12807

    CAS  PubMed  Google Scholar 

  • Sala-Rabanal M, Wang S, Nichols CG (2012) On the potential interactions between non-selective cation channel TRPM4 and the sulfonylurea receptor SUR1. J Biol Chem 287:8746–8756

    CAS  PubMed Central  PubMed  Google Scholar 

  • Saliez J, Bouzin C, Rath G, Ghisdal P, Desjardins F, Rezzani R, Rodella LF, Vriens J, Nilius B, Feron O et al (2008) Role of caveolar compartmentation in endothelium-derived hyperpolarizing factor-mediated relaxation: Ca2+ signals and gap junction function are regulated by caveolin in endothelial cells. Circulation 117:1065–1074

    CAS  PubMed  Google Scholar 

  • Samways DS, Egan TM (2011) Calcium-dependent decrease in the single-channel conductance of TRPV1. Pflugers Archiv 462:681–691

    CAS  PubMed Central  PubMed  Google Scholar 

  • Schindl R, Fritsch R, Jardin I, Frischauf I, Kahr H, Muik M, Riedl MC, Groschner K, Romanin C (2012) Canonical transient receptor potential (TRPC) 1 acts as a negative regulator for vanilloid TRPV6 mediated Ca2+ influx. J Biol Chem 287:35612–33520

    CAS  PubMed Central  PubMed  Google Scholar 

  • Schmidt TM, Chen SK, Hattar S (2011) Intrinsically photosensitive retinal ganglion cells: many subtypes, diverse functions. Trends Neurosci 34:572–580

    CAS  PubMed Central  PubMed  Google Scholar 

  • Schwenk J, Harmel N, Brechet A, Zolles G, Berkefeld H, Muller CS, Bildl W, Baehrens D, Huber B, Kulik A et al (2012) High-resolution proteomics unravel architecture and molecular diversity of native AMPA receptor complexes. Neuron 74:621–633

    CAS  PubMed  Google Scholar 

  • Sedgwick SG, Smerdon SJ (1999) The ankyrin repeat: a diversity of interactions on a common structural framework. Trends Biochem Sci 24:311–316

    CAS  PubMed  Google Scholar 

  • Shen WL, Kwon Y, Adegbola AA, Luo J, Chess A, Montell C (2011) Function of rhodopsin in temperature discrimination in Drosophila. Science 331:1333–1336

    CAS  PubMed  Google Scholar 

  • Shi J, Birnbaumer L, Large WA, Albert AP (2013a) Myristoylated alanine-rich C kinase substrate coordinates native TRPC1 channel activation by phosphatidylinositol 4,5-bisphosphate and protein kinase C in vascular smooth muscle. FASEB J 28:244–255

    PubMed  Google Scholar 

  • Shi M, Du F, Liu Y, Li L, Cai J, Zhang GF, Xu XF, Lin T, Cheng HR, Liu XD et al (2013b) Glial cell-expressed mechanosensitive channel TRPV4 mediates infrasound-induced neuronal impairment. Acta neuropathologica 126:725–739

    CAS  PubMed  Google Scholar 

  • Shibasaki K, Suzuki M, Mizuno A, Tominaga M (2007) Effects of body temperature on neural activity in the hippocampus: regulation of resting membrane potentials by transient receptor potential vanilloid 4. J Neurosci 27:1566–1575

    CAS  PubMed  Google Scholar 

  • Sigg D, Bezanilla F (1997) Total charge movement per channel. The relation between gating charge displacement and the voltage sensitivity of activation. J Gen Physiol 109:27–39

    CAS  PubMed Central  PubMed  Google Scholar 

  • Simard JM, Kahle KT, Gerzanich V (2010) Molecular mechanisms of microvascular failure in central nervous system injury-synergistic roles of NKCC1 and SUR1/TRPM4. J Neurosurg 113:622–629

    CAS  PubMed Central  PubMed  Google Scholar 

  • Singh BB, Liu X, Tang J, Zhu MX, Ambudkar IS (2002) Calmodulin regulates Ca(2+)-dependent feedback inhibition of store-operated Ca(2+) influx by interaction with a site in the C terminus of TrpC1. Mol Cell 9:739–750

    CAS  PubMed  Google Scholar 

  • Starace DM, Bezanilla F (2004) A proton pore in a potassium channel voltage sensor reveals a focused electric field. Nature 427:548–553

    CAS  PubMed  Google Scholar 

  • Storch U, Forst AL, Philipp M, Gudermann T, Mederos YSM (2012) TRPC1 reduces the calcium permeability in heteromeric channel complexes. J Biol Chem 287:3530–3540

    CAS  PubMed Central  PubMed  Google Scholar 

  • Straub I, Krugel U, Mohr F, Teichert J, Rizun O, Konrad M, Oberwinkler J, Schaefer M (2013a) Flavanones that selectively inhibit TRPM3 attenuate thermal nociception in vivo. Mol Pharmacol 84:736–750

    CAS  PubMed  Google Scholar 

  • Straub I, Mohr F, Stab J, Konrad M, Philipp S, Oberwinkler J, Schaefer M (2013b) Citrus fruit and fabacea secondary metabolites potently and selectively block TRPM3. Br J Pharmacol 168:1835–1850

    CAS  PubMed Central  PubMed  Google Scholar 

  • Strotmann R, Schultz G, Plant TD (2003) Ca2+-dependent potentiation of the nonselective cation channel TRPV4 is mediated by a carboxy terminal calmodulin binding site. J Biol Chem 278:26541–26549

    CAS  PubMed  Google Scholar 

  • Strotmann R, Semtner M, Kepura F, Plant TD, Schoneberg T (2010) Interdomain interactions control Ca-dependent potentiation in the cation channel TRPV4. PLoS One 5:e10580

    PubMed Central  PubMed  Google Scholar 

  • Strubing C, Krapivinsky G, Krapivinsky L, Clapham DE (2001) TRPC1 and TRPC5 form a novel cation channel in mammalian brain. Neuron 29:645–655

    CAS  PubMed  Google Scholar 

  • Sun HS, Jackson MF, Martin LJ, Jansen K, Teves L, Cui H, Kiyonaka S, Mori Y, Jones M, Forder JP et al (2009) Suppression of hippocampal TRPM7 protein prevents delayed neuronal death in brain ischemia. Nat Neurosci 12:1300–1307

    CAS  PubMed  Google Scholar 

  • Swoap SJ (2013) Thermoregulation: an orphan receptor finds its way in the cold. Curr Biol 22:R17–18

    Google Scholar 

  • Tang Z, Kim A, Masuch T, Park K, Weng H, Wetzel C, Dong X (2013) Pirt functions as an endogenous regulator of TRPM8. Nat Commun 4:2179

    PubMed Central  PubMed  Google Scholar 

  • Tew KD, Monks A, Barone L, Rosser D, Akerman G, Montali JA, Wheatley JB, Schmidt DE Jr (1996) Glutathione-associated enzymes in the human cell lines of the National Cancer Institute Drug Screening Program. Mol Pharmacol 50:149–159

    CAS  PubMed  Google Scholar 

  • Tombola F, Pathak MM, Gorostiza P, Isacoff EY (2007) The twisted ion-permeation pathway of a resting voltage-sensing domain. Nature 445:546–549

    CAS  PubMed  Google Scholar 

  • Tsiokas L, Arnould T, Zhu C, Kim E, Walz G, Sukhatme V (1999) Specific association of the gene product of PKD2 with the TRPC1 channel. Proc Natl Acad Sci U S A 96:3934–3939

    CAS  PubMed Central  PubMed  Google Scholar 

  • Tsuruda PR, Julius D, Minor DL Jr (2006) Coiled coils direct assembly of a cold-activated TRP channel. Neuron 51:201–212

    CAS  PubMed Central  PubMed  Google Scholar 

  • Tsvilovskyy VV, Zholos AV, Aberle T, Philipp SE, Dietrich A, Zhu MX, Birnbaumer L, Freichel M, Flockerzi V (2009) Deletion of TRPC4 and TRPC6 in mice impairs smooth muscle contraction and intestinal motility in vivo. Gastroenterology 137:1415–1424

    PubMed Central  PubMed  Google Scholar 

  • Uemura T, Kudoh J, Noda S, Kanba S, Shimizu N (2005) Characterization of human and mouse TRPM2 genes: identification of a novel N-terminal truncated protein specifically expressed in human striatum. Biochem Biophys Res Commun 328:1232–1243

    CAS  PubMed  Google Scholar 

  • Ufret-Vincenty CA, Klein RM, Hua L, Angueyra J, Gordon SE (2011) Localization of the PIP2 sensor of TRPV1 ion channels. J Biol Chem 283:26208–26216

    Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • Vay L, Gu C, McNaughton PA (2011) The thermo-TRP ion channel family: properties and therapeutic implications. Br J Pharmacol 165:787–801

    Google Scholar 

  • Vennekens R, Hoenderop JG, Prenen J, Stuiver M, Willems PH, Droogmans G, Nilius B, Bindels RJ (2000) Permeation and gating properties of the novel epithelial Ca2+ channel. J Biol Chem 275:3963–3969

    CAS  PubMed  Google Scholar 

  • Vennekens R, Menigoz A, Nilius B (2012) TRPs in the brain. Rev Physiol Biochem Pharmacol 163:27–64

    PubMed  Google Scholar 

  • Voets T (2012) Quantifying and modeling the temperature-dependent gating of TRP channels. Rev Physiol Biochem Pharmacol 162:91–119

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Voets T, Owsianik G, Janssens A, Talavera K, Nilius B (2007) TRPM8 voltage sensor mutants reveal a mechanism for integrating thermal and chemical stimuli. Nat Chem Biol 3:174–182

    CAS  PubMed  Google Scholar 

  • Vriens J, Owsianik G, Fisslthaler B, Suzuki M, Janssens A, Voets T, Morisseau C, Hammock BD, Fleming I, Busse R, Nilius B (2005) Modulation of the Ca2 permeable cation channel TRPV4 by cytochrome P450 epoxygenases in vascular endothelium. Circ Res 97:908–915

    CAS  PubMed  Google Scholar 

  • Vriens J, Owsianik G, Hofmann T, Philipp SE, Stab J, Chen X, Benoit M, Xue F, Janssens A, Kerselaers S et al (2011) TRPM3 is a nociceptor channel INVOLVED in the detection of noxious heat. Neuron 70:482–494

    CAS  PubMed  Google Scholar 

  • Vriens J, Held K, Janssens A, Tóth BI, Kerselaers S, Nilius B, Vennekens R, Voets T (2014) Opening of an alternative ion permeation pathway in a nociceptor TRP channel. Nature Chem Biol 10:188–195

    CAS  Google Scholar 

  • 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

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wang S, Poon K, Oswald RE, Chuang HH (2010) Distinct modulations of human capsaicin receptor by protons and magnesium through different domains. J Biol Chem 285:11547–11156

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wang L, Cvetkov TL, Chance MR, Moiseenkova-Bell VY (2012) Identification of in vivo disulfide conformation of the TRPA1 ion channel. J Biol Chem 287:6169–6176

    CAS  PubMed Central  PubMed  Google Scholar 

  • Watanabe H, Davis JB, Smart D, Jerman JC, Smith GD, Hayes P, Vriens J, Cairns W, Wissenbach U, Prenen J et al (2002) Activation of TRPV4 channels (hVRL-2/mTRP12) by phorbol derivatives. J Biol Chem 277:13569–13577

    CAS  PubMed  Google Scholar 

  • Wetsel WC (2011) Sensing hot and cold with TRP channels. Int J Hyperthermia 27:388–398

    CAS  PubMed  Google Scholar 

  • Wheeler GL, Brownlee C (2008) Ca(2+) signalling in plants and green algae - changing channels. Trends Plant Sci 13:506–514

    CAS  PubMed  Google Scholar 

  • Whorton MR, MacKinnon R (2011) Crystal structure of the mammalian GIRK2 K+ channel and gating regulation by G proteins, PIP2, and sodium. Cell 147:199–208

    CAS  PubMed Central  PubMed  Google Scholar 

  • Woo SK, Kwon MS, Ivanov A, Gerzanich V, Simard JM (2013) The sulfonylurea receptor 1 (Sur1) - transient receptor potential melastatin 4 (Trpm4) channel. J Biol Chem 288:3655–3667

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wu LJ, Sweet TB, Clapham DE (2010) International Union of Basic and Clinical Pharmacology. LXXVI. Current progress in the mammalian TRP ion channel family. Pharmacol Rev 62:381–404

    CAS  PubMed Central  PubMed  Google Scholar 

  • Xiao B, Dubin AE, Bursulaya B, Viswanath V, Jegla TJ, Patapoutian A (2008a) Identification of the transmembrane domain five as a critical molecular determinant of menthol sensitivity in mammalian TRPA1 channels. J Neurosci 28:9640–9651

    CAS  PubMed Central  PubMed  Google Scholar 

  • Xiao R, Tang J, Wang C, Colton CK, Tian J, Zhu MX (2008b) Calcium plays a central role in the sensitization of TRPV3 channel to repetitive stimulations. J Biol Chem 283:6162–6174

    CAS  PubMed Central  PubMed  Google Scholar 

  • Xiao R, Tian J, Tang J, Zhu MX (2008c) The TRPV3 mutation associated with the hairless phenotype in rodents is constitutively active. Cell Calcium 43:334–343

    CAS  PubMed Central  PubMed  Google Scholar 

  • Xiao B, Coste B, Mathur J, Patapoutian A (2011) Temperature-dependent STIM1 activation induces Ca(2+) influx and modulates gene expression. Nat Chem Biol 7:351–358

    CAS  PubMed Central  PubMed  Google Scholar 

  • 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 B Neuropsychiatr Genet 141:36–43

    Google Scholar 

  • Xu C, Li PP, Cooke RG, Parikh SV, Wang K, Kennedy JL, Warsh JJ (2009) TRPM2 variants and bipolar disorder risk: confirmation in a family-based association study. Bipolar Disord 11:1–10

    PubMed  Google Scholar 

  • Xue T, Do MT, Riccio A, Jiang Z, Hsieh J, Wang HC, Merbs SL, Welsbie DS, Yoshioka T, Weissgerber P et al (2011) Melanopsin signalling in mammalian iris and retina. Nature 479:67–73

    CAS  PubMed Central  PubMed  Google Scholar 

  • Yamaguchi H, Matsushita M, Nairn AC, Kuriyan J (2001) Crystal structure of the atypical protein kinase domain of a TRP channel with phosphotransferase activity. Mol Cell 7:1047–1057

    CAS  PubMed  Google Scholar 

  • Ye L, Kleiner S, Wu J, Sah R, Gupta RK, Banks AS, Cohen P, Khandekar MJ, Bostrom P, Mepani RJ et al (2012) TRPV4 is a regulator of adipose oxidative metabolism, inflammation, and energy homeostasis. Cell 151:96–110

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ye L, Wu J, Cohen P, Kazak L, Khandekar MJ, Jedrychowski MP, Zeng X, Gygi SP, Spiegelman BM (2013) Fat cells directly sense temperature to activate thermogenesis. Proc Natl Acad Sci U S A 110:12480–12485

    CAS  PubMed Central  PubMed  Google Scholar 

  • Yokoyama S, Altun A, Denardo DF (2011) Molecular convergence of infrared vision in snakes. Mol Biol Evol 28:45–48

    CAS  PubMed Central  PubMed  Google Scholar 

  • Yu Y, Ulbrich MH, Li MH, Buraei Z, Chen XZ, Ong AC, Tong L, Isacoff EY, Yang J (2009) Structural and molecular basis of the assembly of the TRPP2/PKD1 complex. Proc Natl Acad Sci USA 106:11558–11563

    CAS  PubMed Central  PubMed  Google Scholar 

  • Yuan JP, Zeng W, Huang GN, Worley PF, Muallem S (2007) STIM1 heteromultimerizes TRPC channels to determine their function as store-operated channels. Nat Cell Biol 9:636–645

    CAS  PubMed Central  PubMed  Google Scholar 

  • Zagranichnaya TK, Wu X, Villereal ML (2005) Endogenous TRPC1, TRPC3, and TRPC7 proteins combine to form native store-operated channels in HEK-293 cells. J Biol Chem 280:29559–29569

    CAS  PubMed  Google Scholar 

  • Zhang DX, Gutterman DD (2010) TRP channel activation and endothelium-dependent dilation in the systemic circulation. J Cardiovasc Pharmacol 52:133–139

    Google Scholar 

  • Zhang F, Liu S, Yang F, Zheng J, Wang K (2011) Identification of a tetrameric assembly domain in the C-terminus of heat-activated TRPV1 channels. J Biol Chem 286:15308–15316

    CAS  PubMed Central  PubMed  Google Scholar 

  • Zhang X, Li X, Xu H (2012) Phosphoinositide isoforms determine compartment-specific ion channel activity. Proc Natl Acad Sci U S A 109:11384–11389

    CAS  PubMed Central  PubMed  Google Scholar 

  • Zheng J (2013) Molecular mechanism of TRP channels. Compr Physiol 3:221–242

    PubMed Central  PubMed  Google Scholar 

  • Zholos AV, Zholos AA, Bolton TB (2004) G-protein-gated TRP-like cationic channel activated by muscarinic receptors: effect of potential on single-channel gating. J Gen Physiol 123:581–598

    CAS  PubMed Central  PubMed  Google Scholar 

  • Zhou Y, Suzuki Y, Uchida K, Tominaga M (2013) Identification of a splice variant of mouse TRPA1 that regulates TRPA1 activity. Nat Commun 4:2408

    Google Scholar 

  • Zhu MX (2005) Multiple roles of calmodulin and other Ca(2+)-binding proteins in the functional regulation of TRP channels. Pflugers Archiv 451:105–115

    CAS  PubMed  Google Scholar 

  • Zhu X, Chu PB, Peyton M, Birnbaumer L (1995) Molecular cloning of a widely expressed human homologue for the Drosophila trp gene. FEBS Lett 373:193–198

    CAS  PubMed  Google Scholar 

  • Zhu X, Jiang M, Peyton M, Boulay G, Hurst R, Stefani E, Birnbaumer L (1996) trp, a novel mammalian gene family essential for agonist-activated capacitative Ca2+ entry. Cell 85:661–671

    CAS  PubMed  Google Scholar 

  • Zhu Z, Luo Z, Ma S, Liu D (2010) TRP channels and their implications in metabolic diseases. Pflugers Arch 461:211–223

    PubMed  Google Scholar 

  • Zhu J, Yu Y, Ulbrich MH, Li MH, Isacoff EY, Honig B, Yang J (2011) Structural model of the TRPP2/PKD1 C-terminal coiled-coil complex produced by a combined computational and experimental approach. Proc Natl Acad Sci U S A 108:10133–10138

    CAS  PubMed Central  PubMed  Google Scholar 

  • Zitt C, Zobel A, Obukhov AG, Harteneck C, Kalkbrenner F, Lückhoff A, Schultz G (1996) Cloning and functional expression of a human Ca2+-permeable cation channel activated by calcium store depletion. Neuron 16:1189–1196

    CAS  PubMed  Google Scholar 

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  1. Department Cell Mol Medicine, Laboratory Ion Channel Research, KU Leuven, Campus Gasthuisberg, O&N 1, Herestraat 49-Bus 802, 3000, Leuven, Belgium

    Bernd Nilius

  2. Universität des Saarlandes, Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Gebäude 46, 66421, Homburg, Germany

    Veit Flockerzi

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  1. Bernd Nilius
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  1. Laboratory Ion Channel Research, Campus Gasthuisberg, KU Leuven Department, Cell Mol Medicin, Leuven, Belgium

    Bernd Nilius

  2. Pharmakologie und Toxikologie, Universität des Saarlandes, Institut für Experimentelle u. Klinische, Homburg, Germany

    Veit Flockerzi

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Nilius, B., Flockerzi, V. (2014). What Do We Really Know and What Do We Need to Know: Some Controversies, Perspectives, and Surprises. In: Nilius, B., Flockerzi, V. (eds) Mammalian Transient Receptor Potential (TRP) Cation Channels. Handbook of Experimental Pharmacology, vol 223. Springer, Cham. https://doi.org/10.1007/978-3-319-05161-1_20

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