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Annual Review of Physiology

Volume 85, 2023

Molecular Physiology of TRPV Channels: Controversies and Future Challenges

Abstract

The ability to detect stimuli from the environment plays a pivotal role in our survival. The molecules that allow the detection of such signals include ion channels, which are proteins expressed in different cells and organs. Among these ion channels, the transient receptor potential (TRP) family responds to the presence of diverse chemicals, temperature, and osmotic changes, among others. This family of ion channels includes the TRPV or vanilloid subfamily whose members serve several physiological functions. Although these proteins have been studied intensively for the last two decades, owing to their structural and functional complexities, a number of controversies regarding their function still remain. Here, we discuss some salient features of their regulation in light of these controversies and outline some of the efforts pushing the field forward.

Keyword(s): function, ion channels, pain, physiology, structure, TRP channels
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/content/journals/10.1146/annurev-physiol-030222-012349
2023-02-10
2024-04-25
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Literature Cited

  1. 1.
    Wu L-J, Sweet T-B, Clapham DE. 2010. International Union of Basic and Clinical Pharmacology. LXXVI. Current progress in the mammalian TRP ion channel family. Pharmacol. Rev. 62:3381–404
     [Google Scholar]
  2. 2.
    Sidi S, Friedrich RW, Nicolson T. 2003. NompC TRP channel required for vertebrate sensory hair cell mechanotransduction. Science 301:562996–99
     [Google Scholar]
  3. 3.
    Walker RG, Willingham AT, Zuker CS. 2000. A Drosophila mechanosensory transduction channel. Science 287:54612229–34
     [Google Scholar]
  4. 4.
    Cosens DJ, Manning A. 1969. Abnormal electroretinogram from a Drosophila mutant. Nature 224:5216285–87
     [Google Scholar]
  5. 5.
    Minke B, Wu C-F, Pak WL. 1975. Induction of photoreceptor voltage noise in the dark in Drosophila mutant. Nature 258:553084–87
     [Google Scholar]
  6. 6.
    Minke B. 1977. Drosophila mutant with a transducer defect. Biophys. Struct. Mech. 3:159–64
     [Google Scholar]
  7. 7.
    Minke B. 1982. Light-induced reduction in excitation efficiency in the trp mutant of Drosophila. J. Gen. Physiol. 79:3361–85
     [Google Scholar]
  8. 8.
    Montell C, Rubin GM. 1989. Molecular characterization of the Drosophila trp locus: a putative integral membrane protein required for phototransduction. Neuron 2:41313–23
     [Google Scholar]
  9. 9.
    Wong F, Hokanson KM, Chang LT. 1985. Molecular basis of an inherited retinal defect in Drosophila. Investig. Ophthalmol. Vis. Sci. 26:2243–46
     [Google Scholar]
  10. 10.
    Wong F, Schaefer EL, Roop BC, LaMendola JN, Johnson-Seaton D, Shao D. 1989. Proper function of the Drosophila trp gene product during pupal development is important for normal visual transduction in the adult. Neuron 3:181–94
     [Google Scholar]
  11. 11.
    Hardie RC, Minke B. 1992. The trp gene is essential for a light-activated Ca2+ channel in Drosophila photoreceptors. Neuron 8:4643–51
     [Google Scholar]
  12. 12.
    Liu CH, Wang T, Postma M, Obukhov AG, Montell C, Hardie RC. 2007. In vivo identification and manipulation of the Ca2+ selectivity filter in the Drosophila transient receptor potential channel. J. Neurosci. 27:3604–15
     [Google Scholar]
  13. 13.
    Wes PD, Chevesich J, Jeromin A, Rosenberg C, Stetten G, Montell C. 1995. TRPC1, a human homolog of a Drosophila store-operated channel. PNAS 92:219652–56
     [Google Scholar]
  14. 14.
    Zhu X, Chu PB, Peyton M, Birnbaumer L 1995. Molecular cloning of a widely expressed human homologue for the Drosophila trp gene. FEBS Lett. 373:3193–98
     [Google Scholar]
  15. 15.
    Gilmore MM, Green BG. 1993. Sensory irritation and taste produced by NaCl and citric acid: effects of capsaicin desensitization. Chem. Senses 18:3257–72
     [Google Scholar]
  16. 16.
    Karrer T, Bartoshuk L. 1991. Capsaicin desensitization and recovery on the human tongue. Physiol. Behav. 49:4757–64
     [Google Scholar]
  17. 17.
    Bevan S, Geppetti P. 1994. Protons: small stimulants of capsaicin-sensitive sensory nerves. Trends Neurosci. 17:12509–12
     [Google Scholar]
  18. 18.
    Vlachová V, Vyklický L. 1993. Capsaicin-induced membrane currents in cultured sensory neurons of the rat. Physiol. Res. 42:5301–11
     [Google Scholar]
  19. 19.
    Liu L, Simon SA. 1996. Similarities and differences in the currents activated by capsaicin, piperine, and zingerone in rat trigeminal ganglion cells. J. Neurophysiol. 76:31858–69
     [Google Scholar]
  20. 20.
    Cesare P, McNaughton P. 1996. A novel heat-activated current in nociceptive neurons and its sensitization by bradykinin. PNAS 93:2615435–39
     [Google Scholar]
  21. 21.
    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 389:6653816–24
     [Google Scholar]
  22. 22.
    Caterina MJ, Rosen TA, Tominaga M, Brake AJ, Julius D 1999. A capsaicin-receptor homologue with a high threshold for noxious heat. Nature 398:6726436–41
     [Google Scholar]
  23. 23.
    Delany NS, Hurle M, Facer P, Alnadaf T, Plumpton C et al. 2001. Identification and characterization of a novel human vanilloid receptor-like protein, VRL-2. Physiol. Genom. 4:3165–74
     [Google Scholar]
  24. 24.
    Hoenderop JGJ, van der Kemp AWCM, Hartog A, van de Graaf SFJ, van Os CH et al. 1999. Molecular identification of the apical Ca2+ channel in 1,25-dihydroxyvitamin D3-responsive epithelia. J. Biol. Chem. 274:138375–78
     [Google Scholar]
  25. 25.
    Liedtke W, Choe Y, Martí-Renom MA, Bell AM, Denis CS et al. 2000. Vanilloid receptor-related osmotically activated channel (VR-OAC), a candidate vertebrate osmoreceptor. Cell 103:3525–35
     [Google Scholar]
  26. 26.
    Liedtke W, Friedman JM. 2003. Abnormal osmotic regulation in trpv4−/− mice. PNAS 100:2313698–703
     [Google Scholar]
  27. 27.
    Liu L, Li Y, Wang R, Yin C, Dong Q et al. 2007. Drosophila hygrosensation requires the TRP channels water witch and nanchung. Nature 450:7167294–98
     [Google Scholar]
  28. 28.
    Peng J-B, Chen X-Z, Berger UV, Vassilev PM, Tsukaguchi H et al. 1999. Molecular cloning and characterization of a channel-like transporter mediating intestinal calcium absorption. J. Biol. Chem. 274:3222739–46
     [Google Scholar]
  29. 29.
    Servin-Vences MR, Moroni M, Lewin GR, Poole K. 2017. Direct measurement of TRPV4 and PIEZO1 activity reveals multiple mechanotransduction pathways in chondrocytes. eLife 6:e21074
     [Google Scholar]
  30. 30.
    Xu H, Ramsey IS, Kotecha SA, Moran MM, Chong JA et al. 2002. TRPV3 is a calcium-permeable temperature-sensitive cation channel. Nature 418:6894181–86
     [Google Scholar]
  31. 31.
    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 141:5834–45
     [Google Scholar]
  32. 32.
    Morales-Lázaro SL, Serrano-Flores B, Llorente I, Hernández-García E, González-Ramírez R et al. 2014. Structural determinants of the transient receptor potential 1 (TRPV1) channel activation by phospholipid analogs. J. Biol. Chem. 289:3524079–90
     [Google Scholar]
  33. 33.
    Nieto-Posadas A, Picazo-Juárez G, Llorente I, Jara-Oseguera A, Morales-Lázaro S et al. 2012. Lysophosphatidic acid directly activates TRPV1 through a C-terminal binding site. Nat. Chem. Biol. 8:178–85
     [Google Scholar]
  34. 34.
    Ho C-Y, Gu Q, Lin YS, Lee L-Y. 2001. Sensitivity of vagal afferent endings to chemical irritants in the rat lung. Respir. Physiol. 127:2–3113–24
     [Google Scholar]
  35. 35.
    Ristoiu V, Shibasaki K, Uchida K, Zhou Y, Ton B-HT et al. 2011. Hypoxia-induced sensitization of transient receptor potential vanilloid 1 involves activation of hypoxia-inducible factor-1 alpha and PKC. Pain 152:4936–45
     [Google Scholar]
  36. 36.
    Denda M, Fuziwara S, Inoue K, Denda S, Akamatsu H et al. 2001. Immunoreactivity of VR1 on epidermal keratinocyte of human skin. Biochem. Biophys. Res. Commun. 285:51250–52
     [Google Scholar]
  37. 37.
    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. 30:134601–12
     [Google Scholar]
  38. 38.
    Sato M, Sobhan U, Tsumura M, Kuroda H, Soya M et al. 2013. Hypotonic-induced stretching of plasma membrane activates transient receptor potential vanilloid channels and sodium-calcium exchangers in mouse odontoblasts. J. Endod. 39:6779–87
     [Google Scholar]
  39. 39.
    Katanosaka Y, Iwasaki K, Ujihara Y, Takatsu S, Nishitsuji K et al. 2014. TRPV2 is critical for the maintenance of cardiac structure and function in mice. Nat. Commun. 5:13932
     [Google Scholar]
  40. 40.
    Peier AM, Reeve AJ, Andersson DA, Moqrich A, Earley TJ et al. 2002. A heat-sensitive TRP channel expressed in keratinocytes. Science 296:55752046–49
     [Google Scholar]
  41. 41.
    Facer P, Casula MA, Smith GD, Benham CD, Chessell IP et al. 2007. Differential expression of the capsaicin receptor TRPV1 and related novel receptors TRPV3, TRPV4 and TRPM8 in normal human tissues and changes in traumatic and diabetic neuropathy. BMC Neurol. 7:11
     [Google Scholar]
  42. 42.
    Nilius B, Bíró T, Owsianik G. 2014. TRPV3: time to decipher a poorly understood family member!. J. Physiol. 592:2295–304
     [Google Scholar]
  43. 43.
    Corrigan MA, Johnson GP, Stavenschi E, Riffault M, Labour M-N, Hoey DA. 2018. TRPV4-mediates oscillatory fluid shear mechanotransduction in mesenchymal stem cells in part via the primary cilium. Sci. Rep. 8:13824
     [Google Scholar]
  44. 44.
    Denda M, Sokabe T, Fukumi-Tominaga T, Tominaga M. 2007. Effects of skin surface temperature on epidermal permeability barrier homeostasis. J. Investig. Dermatol. 127:3654–59
     [Google Scholar]
  45. 45.
    Yang P, Lu P, Luo J, Du L, Feng J et al. 2020. Transient stimulation of TRPV4-expressing keratinocytes promotes hair follicle regeneration in mice. Br. J. Pharmacol. 177:184181–92
     [Google Scholar]
  46. 46.
    Chen Y, Wang Z-L, Yeo M, Zhang Q-J, López-Romero AE et al. 2021. Epithelia-sensory neuron cross talk underlies cholestatic itch induced by lysophosphatidylcholine. Gastroenterology 161:1301–17.e16
     [Google Scholar]
  47. 47.
    Hoenderop JGJ, van Leeuwen JPTM, van der Eerden BCJ, Kersten FFJ, van der Kemp AWCM et al. 2003. Renal Ca2+ wasting, hyperabsorption, and reduced bone thickness in mice lacking TRPV5. J. Clin. Investig. 112:121906–14
     [Google Scholar]
  48. 48.
    Yelshanskaya MV, Nadezhdin KD, Kurnikova MG, Sobolevsky AI. 2021. Structure and function of the calcium-selective TRP channel TRPV6. J. Physiol. 599:102673–97
     [Google Scholar]
  49. 49.
    Kwon DH, Zhang F, Suo Y, Bouvette J, Borgnia MJ, Lee S-Y. 2021. Heat-dependent opening of TRPV1 in the presence of capsaicin. Nat. Struct. Mol. Biol. 28:7554–63
     [Google Scholar]
  50. 50.
    Singh AK, McGoldrick LL, Demirkhanyan L, Leslie M, Zakharian E, Sobolevsky AI. 2019. Structural basis of temperature sensation by the TRP channel TRPV3. Nat. Struct. Mol. Biol. 26:11994–98
     [Google Scholar]
  51. 51.
    Saotome K, Singh AK, Yelshanskaya MV, Sobolevsky AI. 2016. Crystal structure of the epithelial calcium channel TRPV6. Nature 534:7608506–11
     [Google Scholar]
  52. 52.
    Hughes TET, Pumroy RA, Yazici AT, Kasimova MA, Fluck EC et al. 2018. Structural insights on TRPV5 gating by endogenous modulators. Nat. Commun. 9:14198
     [Google Scholar]
  53. 53.
    Cao E, Liao M, Cheng Y, Julius D 2013. TRPV1 structures in distinct conformations reveal activation mechanisms. Nature 504:7478113–18
     [Google Scholar]
  54. 54.
    Zubcevic L, Herzik MA, Chung BC, Liu Z, Lander GC, Lee S-Y. 2016. Cryo-electron microscopy structure of the TRPV2 ion channel. Nat. Struct. Mol. Biol. 23:2180–86
     [Google Scholar]
  55. 55.
    Zubcevic L, Herzik MA, Wu M, Borschel WF, Hirschi M et al. 2018. Conformational ensemble of the human TRPV3 ion channel. Nat. Commun. 9:14773
     [Google Scholar]
  56. 56.
    Deng Z, Paknejad N, Maksaev G, Sala-Rabanal M, Nichols CG et al. 2018. Cryo-EM and X-ray structures of TRPV4 reveal insight into ion permeation and gating mechanisms. Nat. Struct. Mol. Biol. 25:3252–60
     [Google Scholar]
  57. 57.
    Dosey TL, Wang Z, Fan G, Zhang Z, Serysheva II et al. 2019. Structures of TRPV2 in distinct conformations provide insight into role of the pore turret. Nat. Struct. Mol. Biol. 26:140–49
     [Google Scholar]
  58. 58.
    Nadezhdin KD, Neuberger A, Nikolaev YA, Murphy LA, Gracheva EO et al. 2021. Extracellular cap domain is an essential component of the TRPV1 gating mechanism. Nat. Commun. 12:12154
     [Google Scholar]
  59. 59.
    Salazar H, Llorente I, Jara-Oseguera A, García-Villegas R, Munari M et al. 2008. A single N-terminal cysteine in TRPV1 determines activation by pungent compounds from onion and garlic. Nat. Neurosci. 11:3255
     [Google Scholar]
  60. 60.
    Goretzki B, Glogowski NA, Diehl E, Duchardt-Ferner E, Hacker C et al. 2018. Structural basis of TRPV4 N terminus interaction with Syndapin/PACSIN1–3 and PIP2. Structure 26:121583–93.e5
     [Google Scholar]
  61. 61.
    Lau S-Y, Procko E, Gaudet R 2012. Distinct properties of Ca2+-calmodulin binding to N- and C-terminal regulatory regions of the TRPV1 channel. J. Gen. Physiol. 140:5541–55
     [Google Scholar]
  62. 62.
    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. 285:1731–40
     [Google Scholar]
  63. 63.
    Shi D-J, Ye S, Cao X, Zhang R, Wang K. 2013. Crystal structure of the N-terminal ankyrin repeat domain of TRPV3 reveals unique conformation of finger 3 loop critical for channel function. Protein Cell 4:12942–50
     [Google Scholar]
  64. 64.
    Lishko PV, Procko E, Jin X, Phelps CB, Gaudet R 2007. The ankyrin repeats of TRPV1 bind multiple ligands and modulate channel sensitivity. Neuron 54:6905–18
     [Google Scholar]
  65. 65.
    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. Pflügers Arch. 457:177–89
     [Google Scholar]
  66. 66.
    Dai Y, Wang S, Tominaga M, Yamamoto S, Fukuoka T et al. 2007. Sensitization of TRPA1 by PAR2 contributes to the sensation of inflammatory pain. J. Clin. Investig. 117:71979–87
     [Google Scholar]
  67. 67.
    Kim D, Cavanaugh EJ, Simkin D. 2008. Inhibition of transient receptor potential A1 channel by phosphatidylinositol-4,5-bisphosphate. Am. J. Physiol. Cell Physiol. 295:1C92–99
     [Google Scholar]
  68. 68.
    Zhang Z, Okawa H, Wang Y, Liman ER. 2005. Phosphatidylinositol 4,5-bisphosphate rescues TRPM4 channels from desensitization. J. Biol. Chem. 280:4739185–92
     [Google Scholar]
  69. 69.
    Liu D, Liman ER. 2003. Intracellular Ca2+ and the phospholipid PIP2 regulate the taste transduction ion channel TRPM5. PNAS 100:2515160–65
     [Google Scholar]
  70. 70.
    Xie J, Sun B, Du J, Yang W, Chen H-C et al. 2011. Phosphatidylinositol 4,5-bisphosphate (PIP2) controls magnesium gatekeeper TRPM6 activity. Sci. Rep. 1:1146
     [Google Scholar]
  71. 71.
    Runnels LW, Yue L, Clapham DE. 2002. The TRPM7 channel is inactivated by PIP2 hydrolysis. Nat. Cell Biol. 4:5329–36
     [Google Scholar]
  72. 72.
    Rohács T, Lopes CMB, Michailidis I, Logothetis DE. 2005. PI(4,5)P2 regulates the activation and desensitization of TRPM8 channels through the TRP domain. Nat. Neurosci. 8:5626–34
     [Google Scholar]
  73. 73.
    Toth B, Csanady L. 2012. Pore collapse underlies irreversible inactivation of TRPM2 cation channel currents. PNAS 109:3313440–45
     [Google Scholar]
  74. 74.
    Morales-Lázaro SL, Rosenbaum T. 2017. Multiple mechanisms of regulation of transient receptor potential ion channels by cholesterol. Curr. Topics Membr. 80:139–61
     [Google Scholar]
  75. 75.
    Morales-Lázaro SL, Lemus L, Rosenbaum T. 2017. Regulation of thermoTRPs by lipids. Temperature 4:124–40
     [Google Scholar]
  76. 76.
    Saleh SN, Albert AP, Large WA. 2009. Obligatory role for phosphatidylinositol 4,5-bisphosphate in activation of native TRPC1 store-operated channels in vascular myocytes: PIP2 activation of TRPC1 SOCs. J. Physiol. 587:3531–40
     [Google Scholar]
  77. 77.
    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. 137:3271–88
     [Google Scholar]
  78. 78.
    Ma R, Li W-P, Rundle D, Kong J, Akbarali HI, Tsiokas L. 2005. PKD2 Functions as an epidermal growth factor-activated plasma membrane channel. Mol. Cell. Biol. 25:188285–98
     [Google Scholar]
  79. 79.
    Prescott ED, Julius D 2003. A modular PIP2 binding site as a determinant of capsaicin receptor sensitivity. Science 300:56231284–88
     [Google Scholar]
  80. 80.
    Takahashi N, Hamada-Nakahara S, Itoh Y, Takemura K, Shimada A et al. 2014. TRPV4 channel activity is modulated by direct interaction of the ankyrin domain to PI(4,5)P2. Nat. Commun. 5:14994
     [Google Scholar]
  81. 81.
    Andersson DA, Nash M, Bevan S. 2007. Modulation of the cold-activated channel TRPM8 by lysophospholipids and polyunsaturated fatty acids. J. Neurosci. 27:123347–55
     [Google Scholar]
  82. 82.
    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 77:4667–79
     [Google Scholar]
  83. 83.
    Liu B, Hui K, Qin F. 2003. Thermodynamics of heat activation of single capsaicin ion channels VR1. Biophys. J. 85:52988–3006
     [Google Scholar]
  84. 84.
    Harraz OF, Longden TA, Hill-Eubanks D, Nelson MT. 2018. PIP2 depletion promotes TRPV4 channel activity in mouse brain capillary endothelial cells. eLife 7:e38689
     [Google Scholar]
  85. 85.
    Monet M, Lehen'kyi V, Gackiere F, Firlej V, Vandenberghe M et al. 2010. Role of cationic channel TRPV2 in promoting prostate cancer migration and progression to androgen resistance. Cancer Res. 70:31225–35
     [Google Scholar]
  86. 86.
    Pan H-L, Zhang Y-Q, Zhao Z-Q. 2010. Involvement of lysophosphatidic acid in bone cancer pain by potentiation of TRPV1 via PKCe pathway in dorsal root ganglion neurons. Mol. Pain 6:85
     [Google Scholar]
  87. 87.
    Picazo-Juarez G, Romero-Suarez S, Nieto-Posadas A, Llorente I, Jara-Oseguera A et al. 2011. Identification of a binding motif in the S5 helix that confers cholesterol sensitivity to the TRPV1 ion channel. J. Biol. Chem. 286:2824966–76
     [Google Scholar]
  88. 88.
    Morales-Lázaro SL, Llorente I, Sierra-Ramírez F, López-Romero AE, Ortíz-Rentería M et al. 2016. Inhibition of TRPV1 channels by a naturally occurring omega-9 fatty acid reduces pain and itch. Nat. Commun. 7:13092
     [Google Scholar]
  89. 89.
    Shukla S, Jin R, Robustelli J, Zimmerman ZE, Baumgart T 2019. PIP2 reshapes membranes through asymmetric desorption. Biophys. J. 117:5962–74
     [Google Scholar]
  90. 90.
    Klein RM, Ufret-Vincenty CA, Hua L, Gordon SE. 2008. Determinants of molecular specificity in phosphoinositide regulation. J. Biol. Chem. 283:3826208–16
     [Google Scholar]
  91. 91.
    Yao J, Qin F. 2009. Interaction with phosphoinositides confers adaptation onto the TRPV1 pain receptor. PLOS Biol. 7:2e1000046
     [Google Scholar]
  92. 92.
    Ufret-Vincenty CA, Klein RM, Hua L, Angueyra J, Gordon SE. 2011. Localization of the PIP2 sensor of TRPV1 ion channels. J. Biol. Chem. 286:119688–98
     [Google Scholar]
  93. 93.
    Brauchi S, Orta G, Mascayano C, Salazar M, Raddatz N et al. 2007. Dissection of the components for PIP2 activation and thermosensation in TRP channels. PNAS 104:2410246–51
     [Google Scholar]
  94. 94.
    Sun X, Zakharian E. 2015. Regulation of the temperature-dependent activation of transient receptor potential vanilloid 1 (TRPV1) by phospholipids in planar lipid bilayers. J. Biol. Chem. 290:84741–47
     [Google Scholar]
  95. 95.
    Hammond GRV, Fischer MJ, Anderson KE, Holdich J, Koteci A et al. 2012. PI4P and PI(4,5)P2 are essential but independent lipid determinants of membrane identity. Science 337:6095727–30
     [Google Scholar]
  96. 96.
    Winter Z, Buhala A, Ötvös F, Jósvay K, Vizler C et al. 2013. Functionally important amino acid residues in the transient receptor potential vanilloid 1 (TRPV1) ion channel—an overview of the current mutational data. Mol. Pain 9:30
     [Google Scholar]
  97. 97.
    Gao Y, Cao E, Julius D, Cheng Y 2016. TRPV1 structures in nanodiscs reveal mechanisms of ligand and lipid action. Nature 534:7607347–51
     [Google Scholar]
  98. 98.
    Yazici AT, Gianti E, Kasimova MA, Lee B-H, Carnevale V, Rohacs T. 2021. Dual regulation of TRPV1 channels by phosphatidylinositol via functionally distinct binding sites. J. Biol. Chem. 296:100573
     [Google Scholar]
  99. 99.
    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. J. Biol. Chem. 288:4935003–13
     [Google Scholar]
  100. 100.
    Lukacs V, Thyagarajan B, Varnai P, Balla A, Balla T, Rohacs T. 2007. Dual regulation of TRPV1 by phosphoinositides. J. Neurosci. 27:267070–80
     [Google Scholar]
  101. 101.
    Poblete H, Oyarzún I, Olivero P, Comer J, Zuñiga M et al. 2015. Molecular determinants of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) binding to transient receptor potential V1 (TRPV1) channels. J. Biol. Chem. 290:42086–98
     [Google Scholar]
  102. 102.
    Stein AT, Ufret-Vincenty CA, Hua L, Santana LF, Gordon SE. 2006. Phosphoinositide 3-kinase binds to TRPV1 and mediates NGF-stimulated TRPV1 trafficking to the plasma membrane. J. Gen. Physiol. 128:5509–22
     [Google Scholar]
  103. 103.
    Senning EN, Collins MD, Stratiievska A, Ufret-Vincenty CA, Gordon SE. 2014. Regulation of TRPV1 ion channel by phosphoinositide (4,5)-bisphosphate: the role of membrane asymmetry. J. Biol. Chem. 289:1610999–11006
     [Google Scholar]
  104. 104.
    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. 30:4013338–47
     [Google Scholar]
  105. 105.
    Garcia-Elias A, Mrkonjić S, Pardo-Pastor C, Inada H, Hellmich UA et al. 2013. Phosphatidylinositol-4,5-biphosphate-dependent rearrangement of TRPV4 cytosolic tails enables channel activation by physiological stimuli. PNAS 110:239553–58
     [Google Scholar]
  106. 106.
    Balakrishna S, Song W, Achanta S, Doran SF, Liu B et al. 2014. TRPV4 inhibition counteracts edema and inflammation and improves pulmonary function and oxygen saturation in chemically induced acute lung injury. Am. J. Physiol. Lung Cell. Mol. Physiol. 307:2L158–172
     [Google Scholar]
  107. 107.
    Landouré G, Zdebik AA, Martinez TL, Burnett BG, Stanescu HC et al. 2010. Mutations in TRPV4 cause Charcot-Marie-Tooth disease type 2C. Nat. Genet. 42:2170–74
     [Google Scholar]
  108. 108.
    Dang S, van Goor MK, Asarnow D, Wang Y, Julius D et al. 2019. Structural insight into TRPV5 channel function and modulation. PNAS 116:188869–78
     [Google Scholar]
  109. 109.
    McGoldrick LL, Singh AK, Saotome K, Yelshanskaya MV, Twomey EC et al. 2018. Opening of the human epithelial calcium channel TRPV6. Nature 553:7687233–37
     [Google Scholar]
  110. 110.
    Cai R, Liu X, Zhang R, Hofmann L, Zheng W et al. 2020. Autoinhibition of TRPV6 channel and regulation by PIP2. iScience 23:9101444
     [Google Scholar]
  111. 111.
    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. 30:4916536–44
     [Google Scholar]
  112. 112.
    Monet M, Gkika D, Lehen'kyi V, Pourtier A, Vanden Abeele F et al. 2009. Lysophospholipids stimulate prostate cancer cell migration via TRPV2 channel activation. Biochim. Biophys. Acta 1793:3528–39
     [Google Scholar]
  113. 113.
    Chung M-K, Güler AD, Caterina MJ. 2008. TRPV1 shows dynamic ionic selectivity during agonist stimulation. Nat. Neurosci. 11:5555–64
     [Google Scholar]
  114. 114.
    Chung M-K, Güler AD, Caterina MJ. 2005. Biphasic currents evoked by chemical or thermal activation of the heat-gated ion channel, TRPV3. J. Biol. Chem. 280:1615928–41
     [Google Scholar]
  115. 115.
    Nabissi M, Morelli MB, Santoni M, Santoni G. 2013. Triggering of the TRPV2 channel by cannabidiol sensitizes glioblastoma cells to cytotoxic chemotherapeutic agents. Carcinogenesis 34:148–57
     [Google Scholar]
  116. 116.
    Steyger PS, Karasawa T. 2008. Intra-cochlear trafficking of aminoglycosides. Commun. Integr. Biol. 1:2140–42
     [Google Scholar]
  117. 117.
    Virginio C, MacKenzie A, Rassendren FA, North RA, Surprenant A. 1999. Pore dilation of neuronal P2X receptor channels. Nat. Neurosci. 2:4315–21
     [Google Scholar]
  118. 118.
    Li M, Toombes GES, Silberberg SD, Swartz KJ. 2015. Physical basis of apparent pore dilation of ATP-activated P2X receptor channels. Nat. Neurosci. 18:111577–83
     [Google Scholar]
  119. 119.
    Puopolo M, Binshtok AM, Yao G-L, Oh SB, Woolf CJ, Bean BP. 2013. Permeation and block of TRPV1 channels by the cationic lidocaine derivative QX-314. J. Neurophysiol. 109:71704–12
     [Google Scholar]
  120. 120.
    Canul-Sánchez JA, Hernández-Araiza I, Hernández-García E, Llorente I, Morales-Lázaro SL et al. 2018. Different agonists induce distinct single-channel conductance states in TRPV1 channels. J. Gen. Physiol. 150:121735–46
     [Google Scholar]
  121. 121.
    Strotmann R, Harteneck C, Nunnenmacher K, Schultz G, Plant TD. 2000. OTRPC4, a nonselective cation channel that confers sensitivity to extracellular osmolarity. Nat. Cell Biol. 2:10695–702
     [Google Scholar]
  122. 122.
    Pairet N, Mang S, Fois G, Keck M, Kühnbach M et al. 2018. TRPV4 inhibition attenuates stretch-induced inflammatory cellular responses and lung barrier dysfunction during mechanical ventilation. PLOS ONE 13:4e0196055
     [Google Scholar]
  123. 123.
    Mizuno A, Matsumoto N, Imai M, Suzuki M. 2003. Impaired osmotic sensation in mice lacking TRPV4. Am. J. Physiol. Cell Physiol. 285:1C96–101
     [Google Scholar]
  124. 124.
    Servin-Vences MR, Richardson J, Lewin GR, Poole K. 2018. Mechanoelectrical transduction in chondrocytes. Clin. Exp. Pharmacol. Physiol. 45:5481–88
     [Google Scholar]
  125. 125.
    O'Conor CJ, Leddy HA, Benefield HC, Liedtke WB, Guilak F. 2014. TRPV4-mediated mechanotransduction regulates the metabolic response of chondrocytes to dynamic loading. PNAS 111:41316–21
     [Google Scholar]
  126. 126.
    Matthews BD, Thodeti CK, Tytell JD, Mammoto A, Overby DR, Ingber DE. 2010. Ultra-rapid activation of TRPV4 ion channels by mechanical forces applied to cell surface β1 integrins. Integr. Biol. 2:9435–42
     [Google Scholar]
  127. 127.
    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. PNAS 101:1396–401
     [Google Scholar]
  128. 128.
    Thorneloe KS, Sulpizio AC, Lin Z, Figueroa DJ, Clouse AK et al. 2008. N-((1S)-1-{[4-((2S)-2-{[(2,4-dichlorophenyl)sulfonyl]amino}-3-hydroxypropanoyl)-1-piperazinyl]carbonyl}-3-methylbutyl)-1-benzothiophene-2-carboxamide (GSK1016790A), a novel and potent transient receptor potential vanilloid 4 channel agonist induces urinary bladder contraction and hyperactivity: Part I. J. Pharmacol. Exp. Ther. 326:2432–42
     [Google Scholar]
  129. 129.
    Rosenbaum T, Benítez-Angeles M, Sánchez-Hernández R, Morales-Lázaro SL, Hiriart M et al. 2020. TRPV4: a physio and pathophysiologically significant ion channel. Int. J. Mol. Sci. 21:113837
     [Google Scholar]
  130. 130.
    Lamandé SR, Yuan Y, Gresshoff IL, Rowley L, Belluoccio D et al. 2011. Mutations in TRPV4 cause an inherited arthropathy of hands and feet. Nat. Genet. 43:111142–46
     [Google Scholar]
  131. 131.
    Rubin J, Rubin C, Jacobs CR. 2006. Molecular pathways mediating mechanical signaling in bone. Gene 367:1–16
     [Google Scholar]
  132. 132.
    Coste B, Mathur J, Schmidt M, Earley TJ, Ranade S et al. 2010. Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels. Science 330:600055–60
     [Google Scholar]
  133. 133.
    Du G, Li L, Zhang X, Liu J, Hao J et al. 2020. Roles of TRPV4 and piezo channels in stretch-evoked Ca2+ response in chondrocytes. Exp. Biol. Med. 245:3180–89
     [Google Scholar]
  134. 134.
    Sianati S, Schroeter L, Richardson J, Tay A, Lamandé SR, Poole K. 2021. Modulating the mechanical activation of TRPV4 at the cell-substrate interface. Front. Bioeng. Biotechnol. 8:608951
     [Google Scholar]
  135. 135.
    Ciura S, Bourque CW. 2006. Transient receptor potential vanilloid 1 is required for intrinsic osmoreception in organum vasculosum lamina terminalis neurons and for normal thirst responses to systemic hyperosmolality. J. Neurosci. 26:359069–75
     [Google Scholar]
  136. 136.
    Naeini RS, Witty M-F, Séguéla P, Bourque CW. 2006. An N-terminal variant of Trpv1 channel is required for osmosensory transduction. Nat. Neurosci. 9:193–98
     [Google Scholar]
  137. 137.
    Muraki K, Iwata Y, Katanosaka Y, Ito T, Ohya S et al. 2003. TRPV2 is a component of osmotically sensitive cation channels in murine aortic myocytes. Circ. Res. 93:9829–38
     [Google Scholar]
  138. 138.
    Yamamoto M, Chen MZ, Wang Y-J, Sun H-Q, Wei Y et al. 2006. Hypertonic stress increases phosphatidylinositol 4,5-bisphosphate levels by activating PIP5KIβ. J. Biol. Chem. 281:4332630–38
     [Google Scholar]
  139. 139.
    Nikolaev YA, Cox CD, Ridone P, Rohde PR, Cordero-Morales JF et al. 2019. Mammalian TRP ion channels are insensitive to membrane stretch. J. Cell Sci. 132:jcs.238360
     [Google Scholar]
  140. 140.
    Clapham DE, Miller C. 2011. A thermodynamic framework for understanding temperature sensing by transient receptor potential (TRP) channels. PNAS 108:4919492–97
     [Google Scholar]
  141. 141.
    Yao J, Liu B, Qin F. 2010. Kinetic and energetic analysis of thermally activated TRPV1 channels. Biophys. J. 99:61743–53
     [Google Scholar]
  142. 142.
    Sanchez-Moreno A, Guevara-Hernandez E, Contreras-Cervera R, Rangel-Yescas G, Ladron-de-Guevara E et al. 2018. Irreversible temperature gating in trpv1 sheds light on channel activation. eLife 7:e36372
     [Google Scholar]
  143. 143.
    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. 277:4947044–51
     [Google Scholar]
  144. 144.
    Liu B, Qin F. 2016. Use dependence of heat sensitivity of vanilloid receptor TRPV2. Biophys. J. 110:71523–37
     [Google Scholar]
  145. 145.
    Luo L, Wang Y, Li B, Xu L, Kamau PM et al. 2019. Molecular basis for heat desensitization of TRPV1 ion channels. Nat. Commun. 10:12134
     [Google Scholar]
  146. 146.
    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
     [Google Scholar]
  147. 147.
    Moqrich A. 2005. Impaired thermosensation in mice lacking TRPV3, a heat and camphor sensor in the skin. Science 307:57141468–72
     [Google Scholar]
  148. 148.
    Miyamoto T, Dubin AE, Petrus MJ, Patapoutian A. 2009. TRPV1 and TRPA1 mediate peripheral nitric oxide-induced nociception in mice. PLOS ONE 4:10e7596
     [Google Scholar]
  149. 149.
    Grandl J, Hu H, Bandell M, Bursulaya B, Schmidt M et al. 2008. Pore region of TRPV3 ion channel is specifically required for heat activation. Nat. Neurosci. 11:91007–13
     [Google Scholar]
  150. 150.
    Grandl J, Kim SE, Uzzell V, Bursulaya B, Petrus M et al. 2010. Temperature-induced opening of TRPV1 ion channel is stabilized by the pore domain. Nat. Neurosci. 13:6708–14
     [Google Scholar]
  151. 151.
    Cui Y, Yang F, Cao X, Yarov-Yarovoy V, Wang K, Zheng J 2012. Selective disruption of high sensitivity heat activation but not capsaicin activation of TRPV1 channels by pore turret mutations. J. Gen. Physiol. 139:4273–83
     [Google Scholar]
  152. 152.
    Yao J, Liu B, Qin F. 2010. Pore turret of thermal TRP channels is not essential for temperature sensing. PNAS 107:32E125
     [Google Scholar]
  153. 153.
    Zhang F, Jara-Oseguera A, Chang T-H, Bae C, Hanson SM, Swartz KJ. 2018. Heat activation is intrinsic to the pore domain of TRPV1. PNAS 115:2E317–24
     [Google Scholar]
  154. 154.
    Yao J, Liu B, Qin F. 2011. Modular thermal sensors in temperature-gated transient receptor potential (TRP) channels. PNAS 108:2711109–14
     [Google Scholar]
  155. 155.
    Brauchi S. 2006. A hot-sensing cold receptor: C-terminal domain determines thermosensation in transient receptor potential channels. J. Neurosci. 26:184835–40
     [Google Scholar]
  156. 156.
    Jara-Oseguera A, Islas LD 2013. The role of allosteric coupling on thermal activation of thermo-TRP channels. Biophys. J. 104:102160–69
     [Google Scholar]
  157. 157.
    Latorre R, Brauchi S, Orta G, Zaelzer C, Vargas G. 2007. ThermoTRP channels as modular proteins with allosteric gating. Cell Calcium 42:4–5427–38
     [Google Scholar]
  158. 158.
    Cordero-Morales JF, Gracheva EO, Julius D. 2011. Cytoplasmic ankyrin repeats of transient receptor potential A1 (TRPA1) dictate sensitivity to thermal and chemical stimuli. PNAS 108:46E1184–91
     [Google Scholar]
  159. 159.
    Ladrón-de-Guevara E, Dominguez L, Rangel-Yescas GE, Fernández-Velasco DA, Torres-Larios A et al. 2020. The contribution of the ankyrin repeat domain of TRPV1 as a thermal module. Biophys. J. 118:4836–45
     [Google Scholar]
  160. 160.
    Liu B, Yao J, Zhu MX, Qin F. 2011. Hysteresis of gating underlines sensitization of TRPV3 channels. J. Gen. Physiol. 138:5509–20
     [Google Scholar]
  161. 161.
    Nadezhdin KD, Neuberger A, Trofimov YA, Krylov NA, Sinica V et al. 2021. Structural mechanism of heat-induced opening of a temperature-sensitive TRP channel. Nat. Struct. Mol. Biol. 28:7564–72
     [Google Scholar]
  162. 162.
    Palovcak E, Delemotte L, Klein ML, Carnevale V. 2015. Comparative sequence analysis suggests a conserved gating mechanism for TRP channels. J. Gen. Physiol. 146:137–50
     [Google Scholar]
  163. 163.
    Ng LC, Vien TN, Yarov-Yarovoy V, DeCaen PG. 2019. Opening TRPP2 (PKD2L1) requires the transfer of gating charges. PNAS 116:3115540–49
     [Google Scholar]
  164. 164.
    Salazar H, Jara-Oseguera A, Hernandez-Garcia E, Llorente I, Arias-Olguin II et al. 2009. Structural determinants of gating in the TRPV1 channel. Nat. Struct. Mol. Biol. 16:7704–10
     [Google Scholar]
  165. 165.
    Liao M, Cao E, Julius D, Cheng Y 2013. Structure of the TRPV1 ion channel determined by electron cryo-microscopy. Nature 504:7478107–12
     [Google Scholar]
  166. 166.
    Singh AK, McGoldrick LL, Sobolevsky AI. 2018. Structure and gating mechanism of the transient receptor potential channel TRPV3. Nat. Struct. Mol. Biol. 25:9805–13
     [Google Scholar]
  167. 167.
    Jara-Oseguera A, Huffer KE, Swartz KJ. 2019. The ion selectivity filter is not an activation gate in TRPV1–3 channels. eLife 8:e51212
     [Google Scholar]
  168. 168.
    Darré L, Furini S, Domene C. 2015. Permeation and dynamics of an open-activated TRPV1 channel. J. Mol. Biol. 427:2537–49
     [Google Scholar]
  169. 169.
    Sakipov S, Sobolevsky AI, Kurnikova MG. 2018. Ion permeation mechanism in epithelial calcium channel TRVP6. Sci. Rep. 8:5715
     [Google Scholar]
  170. 170.
    Huffer KE, Aleksandrova AA, Jara-Oseguera A, Forrest LR, Swartz KJ. 2020. Global alignment and assessment of TRP channel transmembrane domain structures to explore functional mechanisms. eLife 9:e58660
     [Google Scholar]
  171. 171.
    Jara-Oseguera A, Llorente I, Rosenbaum T, Islas LD. 2008. Properties of the inner pore region of TRPV1 channels revealed by block with quaternary ammoniums. J. Gen. Physiol. 132:5547–62
     [Google Scholar]
  172. 172.
    Oseguera AJ, Islas LD, García-Villegas R, Rosenbaum T. 2007. On the mechanism of TBA block of the TRPV1 channel. Biophys. J. 92:113901–14
     [Google Scholar]
  173. 173.
    Kutzner C, Grubmüller H, De Groot BL, Zachariae U 2011. Computational electrophysiology: the molecular dynamics of ion channel permeation and selectivity in atomistic detail. Biophys. J. 101:4809–17
     [Google Scholar]
  174. 174.
    Numazaki M, Tominaga T, Takeuchi K, Murayama N, Toyooka H, Tominaga M. 2003. Structural determinant of TRPV1 desensitization interacts with calmodulin. PNAS 100:138002–6
     [Google Scholar]
  175. 175.
    Rosenbaum T, Gordon-Shaag A, Munari M, Gordon SE. 2004. Ca2+/calmodulin modulates TRPV1 activation by capsaicin. J. Gen. Physiol. 123:153–62
     [Google Scholar]
  176. 176.
    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. 283:106162–74
     [Google Scholar]
  177. 177.
    Lambers TT, Weidema AF, Nilius B, Hoenderop JGJ, Bindels RJM. 2004. Regulation of the mouse epithelial Ca2+ channel TRPV6 by the Ca2+-sensor calmodulin. J. Biol. Chem. 279:2828855–61
     [Google Scholar]
  178. 178.
    de Groot T, Kovalevskaya NV, Verkaart S, Schilderink N, Felici M et al. 2011. Molecular mechanisms of calmodulin action on TRPV5 and modulation by parathyroid hormone. Mol. Cell. Biol. 31:142845–53
     [Google Scholar]
  179. 179.
    Cao C, Zakharian E, Borbiro I, Rohacs T. 2013. Interplay between calmodulin and phosphatidylinositol 4,5-bisphosphate in Ca2+-induced inactivation of transient receptor potential vanilloid 6 channels. J. Biol. Chem. 288:85278–90
     [Google Scholar]
  180. 180.
    Watanabe H, Vriens J, Janssens A, Wondergem R, Droogmans G, Nilius B. 2003. Modulation of TRPV4 gating by intra- and extracellular Ca2+. Cell Calcium 33:5–6489–95
     [Google Scholar]
  181. 181.
    Singh AK, McGoldrick LL, Twomey EC, Sobolevsky AI. 2018. Mechanism of calmodulin inactivation of the calcium-selective TRP channel TRPV6. Sci. Adv. 4:8eaau6088
     [Google Scholar]
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Molecular Physiology of TRPV Channels: Controversies and Future Challenges
Annual Review of Physiology 85, 293 (2023); https://doi.org/10.1146/annurev-physiol-030222-012349
/content/journals/10.1146/annurev-physiol-030222-012349
/content/journals/10.1146/annurev-physiol-030222-012349
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