Skip to main content

Advertisement

SpringerLink
Log in

TRP Channels in Stroke

  • Review
  • Published:
Neuroscience Bulletin Aims and scope Submit manuscript

Abstract

Ischemic stroke is a devastating disease that affects millions of patients worldwide. Unfortunately, there are no effective medications for mitigating brain injury after ischemic stroke. TRP channels are evolutionally ancient biosensors that detect external stimuli as well as tissue or cellular injury. To date, many members of the TRP superfamily have been reported to contribute to ischemic brain injury, including the TRPC subfamily (1, 3, 4, 5, 6, 7), TRPV subfamily (1, 2, 3, 4) and TRPM subfamily (2, 4, 7). These TRP channels share structural similarities but have distinct channel functions and properties. Their activation during ischemic stroke can be beneficial, detrimental, or even both. In this review, we focus on discussing the interesting features of stroke-related TRP channels and summarizing the underlying cellular and molecular mechanisms responsible for their involvement in ischemic brain injury.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

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

    Article  CAS  PubMed  Google Scholar 

  2. Craig Montell. Molecular characterization of the Drosophila trp locus: A putative integral membrane protein required for phototransduction. Neuron 1989, 2: 1313–1323.

    Article  Google Scholar 

  3. Hardie RC, Minke B. The trp gene is essential for a light-activated Ca2+ channel in Drosophila photoreceptors. Neuron 1992, 8(4): 643–651.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  5. Wes PD, Chevesich J, Jeromin A, Rosenberg C, Stetten G, Montell C. TRPC1, a human homolog of a Drosophila store-operated channel. Proc Natl Acad Sci U S A 1995, 92: 9652–9656.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Clapham DE. TRP channels as cellular sensors. Nature 2003, 426: 517–524.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  8. Nilius B, Owsianik G. The transient receptor potential family of ion channels. Genome Biol 2011, 12: 218.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Himmel NJ, Cox DN. Transient receptor potential channels: Current perspectives on evolution, structure, function and nomenclature. Proc Biol Sci 2020, 287: 20201309.

    PubMed  PubMed Central  Google Scholar 

  10. Cao E. Structural mechanisms of transient receptor potential ion channels. J Gen Physiol 2020, 152: e201811998.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  12. Bouron A, Kiselyov K, Oberwinkler J. Permeation, regulation and control of expression of TRP channels by trace metal ions. Pflugers Arch - Eur J Physiol 2015, 467: 1143–1164.

    Article  CAS  Google Scholar 

  13. Vangeel L, Voets T. Transient receptor potential channels and calcium signaling. Cold Spring Harb Perspect Biol 2019, 11: a035048.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Clapham DE. Calcium signaling. Cell 2007, 131: 1047–1058.

    Article  CAS  PubMed  Google Scholar 

  15. Yue L, Xu H. TRP channels in health and disease at a glance. J Cell Sci 2021, 134: jcs258372.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Koivisto AP, Belvisi MG, Gaudet R, Szallasi A. Advances in TRP channel drug discovery: From target validation to clinical studies. Nat Rev Drug Discov 2022, 21: 41–59.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  18. Saini V, Guada L, Yavagal DR. Global epidemiology of stroke and access to acute ischemic stroke interventions. Neurology 2021, 97: S6–S16.

    Article  PubMed  Google Scholar 

  19. GBD 2019 Stroke Collaborator. Global, regional, and national burden of stroke and its risk factors, 1990-2019: A systematic analysis for the Global Burden of Disease Study 2019. Lancet Neurol 2021, 20: 795–820.

  20. Campbell BCV, De Silva DA, MacLeod MR, Coutts SB, Schwamm LH, Davis SM. Ischaemic stroke. Nat Rev Dis Primers 2019, 5: 70.

    Article  PubMed  Google Scholar 

  21. Muoio V, Persson PB, Sendeski MM. The neurovascular unit - concept review. Acta Physiol (Oxf) 2014, 210: 790–798.

    Article  CAS  PubMed  Google Scholar 

  22. Jäkel S, Dimou L. Glial cells and their function in the adult brain: A journey through the history of their ablation. Front Cell Neurosci 2017, 11: 24.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Xiong Y, Wakhloo AK, Fisher M. Advances in acute ischemic stroke therapy. Circ Res 2022, 130: 1230–1251.

    Article  CAS  PubMed  Google Scholar 

  24. Yu WX, Huang SH, Wang YJ, Zhang M. Recanalization treatment for acute stroke: Can we skip the bridge? Neurosci Bull 2021, 37: 585–587.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Narayan SK, Grace Cherian S, Babu Phaniti P, Babu Chidambaram S, Rachel Vasanthi AH, Arumugam M. Preclinical animal studies in ischemic stroke: Challenges and some solutions. Animal Model Exp Med 2021, 4: 104–115.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Wu QJ, Tymianski M. Targeting NMDA receptors in stroke: New hope in neuroprotection. Mol Brain 2018, 11: 15.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Ikonomidou C, Turski L. Why did NMDA receptor antagonists fail clinical trials for stroke and traumatic brain injury? Lancet Neurol 2002, 1: 383–386.

    Article  CAS  PubMed  Google Scholar 

  28. Zong P, Lin Q, Feng J, Yue L. A systemic review of the integral role of TRPM2 in ischemic stroke: From upstream risk factors to ultimate neuronal death. Cells 2022, 11: 491.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Nadolni W, Zierler S. The channel-kinase TRPM7 as novel regulator of immune system homeostasis. Cells 2018, 7: 109.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Riccio A, Medhurst AD, Mattei C, Kelsell RE, Calver AR, Randall AD, et al. mRNA distribution analysis of human TRPC family in CNS and peripheral tissues. Brain Res Mol Brain Res 2002, 109: 95–104.

    Article  CAS  PubMed  Google Scholar 

  31. Jimenez I, Prado Y, Marchant F, Otero C, Eltit F, Cabello-Verrugio C, et al. TRPM channels in human diseases. Cells 2020, 9: 2604.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Froghi S, Grant CR, Tandon R, Quaglia A, Davidson B, Fuller B. New insights on the role of TRP channels in calcium signalling and immunomodulation: Review of pathways and implications for clinical practice. Clin Rev Allergy Immunol 2021, 60: 271–292.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Thakore P, Earley S. Transient receptor potential channels and endothelial cell calcium signaling. Compr Physiol 2019, 9: 1249–1277.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Verkhratsky A, Reyes RC, Parpura V. TRP channels coordinate ion signalling in astroglia. Rev Physiol Biochem Pharmacol 2014, 166: 1–22.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Çiğ B, Derouiche S, Jiang LH. Editorial: Emerging roles of TRP channels in brain pathology. Front Cell Dev Biol 2021, 9: 705196.

    Article  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  37. Wang H, Cheng X, Tian J, Xiao Y, Tian T, Xu F, et al. TRPC channels: Structure, function, regulation and recent advances in small molecular probes. Pharmacol Ther 2020, 209: 107497.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Veldhuis NA, Poole DP, Grace M, McIntyre P, Bunnett NW. The G protein-coupled receptor-transient receptor potential channel axis: Molecular insights for targeting disorders of sensation and inflammation. Pharmacol Rev 2015, 67: 36–73.

    Article  PubMed  Google Scholar 

  39. Venkatachalam K, Zheng F, Gill DL. Regulation of canonical transient receptor potential (TRPC) channel function by diacylglycerol and protein kinase C. J Biol Chem 2003, 278: 29031–29040.

    Article  CAS  PubMed  Google Scholar 

  40. Saleh SN, Albert AP, Large WA. Obligatory role for phosphatidylinositol 4, 5-bisphosphate in activation of native TRPC1 store-operated channels in vascular myocytes. J Physiol 2009, 587: 531–540.

    Article  CAS  PubMed  Google Scholar 

  41. Tai Y, Jia Y. TRPC channels and neuron development, plasticity, and activities. Adv Exp Med Biol 2017, 976: 95–110.

    Article  CAS  PubMed  Google Scholar 

  42. Negri S, Faris P, Berra-Romani R, Guerra G, Moccia F. Endothelial transient receptor potential channels and vascular remodeling: Extracellular Ca2 + entry for angiogenesis, arteriogenesis and vasculogenesis. Front Physiol 2019, 10: 1618.

    Article  PubMed  Google Scholar 

  43. Jeon J, Bu F, Sun G, Tian JB, Ting SM, Li J, et al. Contribution of TRPC channels in neuronal excitotoxicity associated with neurodegenerative disease and ischemic stroke. Front Cell Dev Biol 2020, 8: 618663.

    Article  PubMed  Google Scholar 

  44. Formoso K, Susperreguy S, Freichel M, Birnbaumer L. RNA-seq analysis reveals TRPC genes to impact an unexpected number of metabolic and regulatory pathways. Sci Rep 2020, 10: 7227.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Partida-Sanchez S, Desai BN, Schwab A, Zierler S. Editorial: TRP channels in inflammation and immunity. Front Immunol 2021, 12: 684172.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Vahidinia Z, Joghataei MT, Beyer C, Karimian M, Tameh AA. G-protein-coupled receptors and ischemic stroke: A focus on molecular function and therapeutic potential. Mol Neurobiol 2021, 58: 4588–4614.

    Article  CAS  PubMed  Google Scholar 

  47. Qin C, Yang S, Chu YH, Zhang H, Pang XW, Chen L, et al. Signaling pathways involved in ischemic stroke: Molecular mechanisms and therapeutic interventions. Signal Transduct Target Ther 2022, 7: 215.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Dietrich A, Fahlbusch M, Gudermann T. Classical transient receptor potential 1 (TRPC1): Channel or channel regulator? Cells 2014, 3: 939–962.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Beech DJ, Muraki K, Flemming R. Non-selective cationic channels of smooth muscle and the mammalian homologues of Drosophila TRP. J Physiol 2004, 559: 685–706.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Lintschinger B, Balzer-Geldsetzer M, Baskaran T, Graier WF, Romanin C, Zhu MX, et al. Coassembly of Trp1 and Trp3 proteins generates diacylglycerol- and Ca2+-sensitive cation channels. J Biol Chem 2000, 275: 27799–27805.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  PubMed  Google Scholar 

  53. Storch U, Forst AL, Philipp M, Gudermann T, Schnitzler MMY. Transient receptor potential channel 1 (TRPC1) reduces calcium permeability in heteromeric channel complexes. J Biol Chem 2012, 287: 3530–3540.

    Article  CAS  PubMed  Google Scholar 

  54. Wang GX, Poo MM. Requirement of TRPC channels in netrin-1-induced chemotropic turning of nerve growth cones. Nature 2005, 434: 898–904.

    Article  CAS  PubMed  Google Scholar 

  55. Shim S, Yuan JP, Kim JY, Zeng W, Huang G, Milshteyn A, et al. Peptidyl-prolyl isomerase FKBP52 controls chemotropic guidance of neuronal growth cones via regulation of TRPC1 channel opening. Neuron 2009, 64: 471–483.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Narayanan KL, Irmady K, Subramaniam S, Unsicker K, Halbach OVB. Evidence that TRPC1 is involved in hippocampal glutamate-induced cell death. Neurosci Lett 2008, 446(2–3): 117–122.

    Article  CAS  PubMed  Google Scholar 

  57. Kim SJ, Kim YS, Yuan JP, Petralia RS, Worley PF, Linden DJ. Activation of the TRPC1 cation channel by metabotropic glutamate receptor mGluR1. Nature 2003, 426: 285–291.

    Article  CAS  PubMed  Google Scholar 

  58. Reiner A, Levitz J. Glutamatergic signaling in the central nervous system: Ionotropic and metabotropic receptors in concert. Neuron 2018, 98: 1080–1098.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Lepannetier S, Gualdani R, Tempesta S, Schakman O, Seghers F, Kreis A, et al. Activation of TRPC1 channel by metabotropic glutamate receptor mGluR5 modulates synaptic plasticity and spatial working memory. Front Cell Neurosci 2018, 12: 318.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Xu N, Meng H, Liu T, Feng Y, Qi Y, Wang H. TRPC1 deficiency exacerbates cerebral ischemia/reperfusion-induced neurological injury by potentiating Nox4-derived reactive oxygen species generation. Cell Physiol Biochem 2018, 51: 1723–1738.

    Article  CAS  PubMed  Google Scholar 

  61. Li Y, Jia YC, Cui K, Li N, Zheng ZY, Wang YZ, et al. Essential role of TRPC channels in the guidance of nerve growth cones by brain-derived neurotrophic factor. Nature 2005, 434: 894–898.

    Article  CAS  PubMed  Google Scholar 

  62. Becker EBE, Oliver PL, Glitsch MD, Banks GT, Achilli F, Hardy A, et al. A point mutation in TRPC3 causes abnormal Purkinje cell development and cerebellar ataxia in moonwalker mice. Proc Natl Acad Sci U S A 2009, 106: 6706–6711.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Jia Y, Zhou J, Tai Y, Wang Y. TRPC channels promote cerebellar granule neuron survival. Nat Neurosci 2007, 10: 559–567.

    Article  CAS  PubMed  Google Scholar 

  64. Hartmann J, Dragicevic E, Adelsberger H, Henning HA, Sumser M, Abramowitz J, et al. TRPC3 channels are required for synaptic transmission and motor coordination. Neuron 2008, 59: 392–398.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Berg AP, Sen N, Bayliss DA. TrpC3/C7 and Slo2.1 are molecular targets for metabotropic glutamate receptor signaling in rat striatal cholinergic interneurons. J Neurosci 2007, 27: 8845–8856.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Zhou J, Du W, Zhou K, Tai Y, Yao H, Jia Y, et al. Critical role of TRPC6 channels in the formation of excitatory synapses. Nat Neurosci 2008, 11: 741–743.

    Article  CAS  PubMed  Google Scholar 

  67. Liu L, Gu L, Chen M, Zheng Y, Xiong X, Zhu S. Novel targets for stroke therapy: Special focus on TRPC channels and TRPC6. Front Aging Neurosci 2020, 12: 70.

    Article  PubMed  PubMed Central  Google Scholar 

  68. Li H, Huang J, Du W, Jia C, Yao H, Wang Y. TRPC6 inhibited NMDA receptor activities and protected neurons from ischemic excitotoxicity. J Neurochem 2012, 123: 1010–1018.

    Article  CAS  PubMed  Google Scholar 

  69. Du W, Huang J, Yao H, Zhou K, Duan B, Wang Y. Inhibition of TRPC6 degradation suppresses ischemic brain damage in rats. J Clin Invest 2010, 120: 3480–3492.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Lin Y, Zhang JC, Fu J, Chen F, Wang J, Wu ZL, et al. Hyperforin attenuates brain damage induced by transient middle cerebral artery occlusion (MCAO) in rats via inhibition of TRPC6 channels degradation. J Cereb Blood Flow Metab 2013, 33: 253–262.

    Article  CAS  PubMed  Google Scholar 

  71. Guo C, Ma Y, Ma S, Mu F, Deng J, Duan J, et al. The role of TRPC6 in the neuroprotection of calycosin against cerebral ischemic injury. Sci Rep 2017, 7: 3039.

    Article  PubMed  PubMed Central  Google Scholar 

  72. Chen J, Li Z, Hatcher JT, Chen QH, Chen L, Wurster RD, et al. Deletion of TRPC6 attenuates NMDA receptor-mediated Ca2+ entry and Ca2+-induced neurotoxicity following cerebral ischemia and oxygen-glucose deprivation. Front Neurosci 2017, 11: 138.

    Article  PubMed  PubMed Central  Google Scholar 

  73. Shen H, Pan J, Pan L, Zhang N. TRPC6 inhibited NMDA current in cultured hippocampal neurons. Neuromol Med 2013, 15: 389–395.

    Article  CAS  Google Scholar 

  74. Chen X, Lu M, He X, Ma L, Birnbaumer L, Liao Y. TRPC3/6/7 knockdown protects the brain from cerebral ischemia injury via astrocyte apoptosis inhibition and effects on NF-кB translocation. Mol Neurobiol 2017, 54: 7555–7566.

    Article  CAS  PubMed  Google Scholar 

  75. Weick JP, Austin Johnson M, Zhang SC. Developmental regulation of human embryonic stem cell-derived neurons by calcium entry via transient receptor potential channels. Stem Cells 2009, 27: 2906–2916.

    Article  CAS  PubMed  Google Scholar 

  76. Stroh O, Freichel M, Kretz O, Birnbaumer L, Hartmann J, Egger V. NMDA receptor-dependent synaptic activation of TRPC channels in olfactory bulb granule cells. J Neurosci 2012, 32: 5737–5746.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Greka A, Navarro B, Oancea E, Duggan A, Clapham DE. TRPC5 is a regulator of hippocampal neurite length and growth cone morphology. Nat Neurosci 2003, 6: 837–845.

    Article  CAS  PubMed  Google Scholar 

  78. Riccio A, Li Y, Moon J, Kim KS, Smith KS, Rudolph U, et al. Essential role for TRPC5 in amygdala function and fear-related behavior. Cell 2009, 137: 761–772.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Riccio A, Li Y, Tsvetkov E, Gapon S, Yao GL, Smith KS, et al. Decreased anxiety-like behavior and Gαq/11-dependent responses in the amygdala of mice lacking TRPC4 channels. J Neurosci 2014, 34: 3653–3667.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Shen N, Wang L, Wu Y, Liu Y, Pei H, Xiang H. Adeno-associated virus packaged TRPC5 gene therapy alleviated spinal cord ischemic reperfusion injury in rats. Neuroreport 2020, 31: 29–36.

    Article  CAS  PubMed  Google Scholar 

  81. Guo J, Li J, Xia L, Wang Y, Zhu J, Du J, et al. Transient receptor potential canonical 5-scramblase signaling complex mediates neuronal phosphatidylserine externalization and apoptosis. Cells 2020, 9: 547.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Shen XY, Gao ZK, Han Y, Yuan M, Guo YS, Bi X. Activation and role of astrocytes in ischemic stroke. Front Cell Neurosci 2021, 15: 755955.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Shirakawa H, Sakimoto S, Nakao K, Sugishita A, Konno M, Iida S, et al. Transient receptor potential canonical 3 (TRPC3) mediates thrombin-induced astrocyte activation and upregulates its own expression in cortical astrocytes. J Neurosci 2010, 30: 13116–13129.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Qin C, Zhou LQ, Ma XT, Hu ZW, Yang S, Chen M, et al. Dual functions of microglia in ischemic stroke. Neurosci Bull 2019, 35: 921–933.

    Article  PubMed  PubMed Central  Google Scholar 

  85. Echeverry S, Rodriguez MJ, Torres YP. Transient receptor potential channels in microglia: Roles in physiology and disease. Neurotox Res 2016, 30: 467–478.

    Article  CAS  PubMed  Google Scholar 

  86. Mizoguchi Y, Kato TA, Seki Y, Ohgidani M, Sagata N, Horikawa H, et al. Brain-derived neurotrophic factor (BDNF) induces sustained intracellular Ca2+ elevation through the up-regulation of surface transient receptor potential 3 (TRPC3) channels in rodent microglia. J Biol Chem 2014, 289: 18549–18555.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Iadecola C, Buckwalter MS, Anrather J. Immune responses to stroke: Mechanisms, modulation, and therapeutic potential. J Clin Invest 2020, 130: 2777–2788.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Candelario-Jalil E, Dijkhuizen RM, Magnus T. Neuroinflammation, stroke, blood-brain barrier dysfunction, and imaging modalities. Stroke 2022, 53: 1473–1486.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Paria BC, Vogel SM, Ahmmed GU, Alamgir S, Shroff J, Malik AB, et al. Tumor necrosis factor-alpha-induced TRPC1 expression amplifies store-operated Ca2+ influx and endothelial permeability. Am J Physiol Lung Cell Mol Physiol 2004, 287: L1303–L1313.

    Article  CAS  PubMed  Google Scholar 

  90. Paria BC, Bair AM, Xue J, Yu Y, Malik AB, Tiruppathi C. Ca2+ influx induced by protease-activated receptor-1 activates a feed-forward mechanism of TRPC1 expression via nuclear factor-kappaB activation in endothelial cells. J Biol Chem 2006, 281: 20715–20727.

    Article  CAS  PubMed  Google Scholar 

  91. Shekhar S, Liu Y, Wang S, Zhang H, Fang X, Zhang J, et al. Novel mechanistic insights and potential therapeutic impact of TRPC6 in neurovascular coupling and ischemic stroke. Int J Mol Sci 2021, 22: 2074.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Duncan LM, Deeds J, Hunter J, Shao J, Holmgren LM, Woolf EA, et al. Down-regulation of the novel gene melastatin correlates with potential for melanoma metastasis. Cancer Res 1998, 58: 1515–1520.

    CAS  PubMed  Google Scholar 

  93. Kraft R, Harteneck C. The mammalian melastatin-related transient receptor potential cation channels: An overview. Pflugers Arch - Eur J Physiol 2005, 451: 204–211.

    Article  CAS  Google Scholar 

  94. Guo J, She J, Zeng W, Chen Q, Bai XC, Jiang Y. Structures of the calcium-activated, non-selective cation channel TRPM4. Nature 2017, 552: 205–209.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Mederos Y, Schnitzler M, Wäring J, Gudermann T, Chubanov V. Evolutionary determinants of divergent calcium selectivity of TRPM channels. FASEB J 2008, 22: 1540–1551.

    Article  Google Scholar 

  96. Launay P, Fleig A, Perraud AL, Scharenberg AM, Penner R, Kinet JP. TRPM4 is a Ca2+-activated nonselective cation channel mediating cell membrane depolarization. Cell 2002, 109: 397–407.

    Article  CAS  PubMed  Google Scholar 

  97. Hofmann T, Chubanov V, Gudermann T, Montell C. TRPM5 is a voltage-modulated and Ca2+activated monovalent selective cation channel. Curr Biol 2003, 13: 1153–1158.

    Article  CAS  PubMed  Google Scholar 

  98. Zhang Y, Hoon MA, Chandrashekar J, Mueller KL, Cook B, Wu D, et al. Coding of sweet, bitter, and umami tastes: Different receptor cells sharing similar signaling pathways. Cell 2003, 112: 293–301.

    Article  CAS  PubMed  Google Scholar 

  99. Duan J, Li Z, Li J, Santa-Cruz A, Sanchez-Martinez S, Zhang J, et al. Structure of full-length human TRPM4. Proc Natl Acad Sci U S A 2018, 115: 2377–2382.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Monteilh-Zoller MK, Hermosura MC, Nadler MJS, Scharenberg AM, Penner R, Fleig A. TRPM7 provides an ion channel mechanism for cellular entry of trace metal ions. J Gen Physiol 2003, 121: 49–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Li M, Jiang J, Yue L. Functional characterization of homo- and heteromeric channel kinases TRPM6 and TRPM7. J Gen Physiol 2006, 127: 525–537.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Kashio M, Tominaga M. TRP channels in thermosensation. Curr Opin Neurobiol 2022, 75: 102591.

    Article  CAS  PubMed  Google Scholar 

  103. Talavera K, Yasumatsu K, Voets T, Droogmans G, Shigemura N, Ninomiya Y, et al. Heat activation of TRPM5 underlies thermal sensitivity of sweet taste. Nature 2005, 438: 1022–1025.

    Article  CAS  PubMed  Google Scholar 

  104. Nagamine K, Kudoh J, Minoshima S, Kawasaki K, Asakawa S, Ito F, et al. Molecular cloning of a novel putative Ca2+ channel protein (TRPC7) highly expressed in brain. Genomics 1998, 54: 124–131.

    Article  CAS  PubMed  Google Scholar 

  105. Perraud AL, Fleig A, Dunn CA, Bagley LA, Launay P, Schmitz C, et al. ADP-ribose gating of the calcium-permeable LTRPC2 channel revealed by Nudix motif homology. Nature 2001, 411: 595–599.

    Article  CAS  PubMed  Google Scholar 

  106. Sano Y, Inamura K, Miyake A, Mochizuki S, Yokoi H, Matsushime H, et al. Immunocyte Ca2+ influx system mediated by LTRPC2. Science 2001, 293: 1327–1330.

    Article  CAS  PubMed  Google Scholar 

  107. Hara Y, Wakamori M, Ishii M, Maeno E, Nishida M, Yoshida T, et al. LTRPC2 Ca2+-permeable channel activated by changes in redox status confers susceptibility to cell death. Mol Cell 2002, 9: 163–173.

    Article  CAS  PubMed  Google Scholar 

  108. Wang L, Fu TM, Zhou Y, Xia S, Greka A, Wu H. Structures and gating mechanism of human TRPM2. Science 2018, 362: eaav4809.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Lange I, Yamamoto S, Partida-Sanchez S, Mori Fleig A, Penner R. TRPM2 functions as a lysosomal Ca2+-release channel in beta cells. Sci Signal 2009, 2: ra23.

    Article  PubMed  PubMed Central  Google Scholar 

  110. Zhong Z, Zhai Y, Liang S, Mori Y, Han R, Sutterwala FS, et al. TRPM2 links oxidative stress to NLRP3 inflammasome activation. Nat Commun 2013, 4: 1611.

    Article  PubMed  Google Scholar 

  111. Mittal M, Nepal S, Tsukasaki Y, Hecquet CM, Soni D, Rehman J, et al. Neutrophil activation of endothelial cell-expressed TRPM2 mediates transendothelial neutrophil migration and vascular injury. Circ Res 2017, 121: 1081–1091.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Almasi S, Kennedy BE, El-Aghil M, Sterea AM, Gujar S, Partida-Sánchez S, et al. TRPM2 channel-mediated regulation of autophagy maintains mitochondrial function and promotes gastric cancer cell survival via the JNK-signaling pathway. J Biol Chem 2018, 293: 3637–3650.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Zhang W, Chu X, Tong Q, Cheung JY, Conrad K, Masker K, et al. A novel TRPM2 isoform inhibits calcium influx and susceptibility to cell death. J Biol Chem 2003, 278: 16222–16229.

    Article  CAS  PubMed  Google Scholar 

  114. Fonfria E, Marshall IC, Boyfield I, Skaper SD, Hughes JP, Owen DE, et al. Amyloid beta-peptide(1–42) and hydrogen peroxide-induced toxicity are mediated by TRPM2 in rat primary striatal cultures. J Neurochem 2005, 95: 715–723.

    Article  CAS  PubMed  Google Scholar 

  115. Kaneko S, Kawakami S, Hara Y, Wakamori M, Itoh E, Minami T, et al. A critical role of TRPM2 in neuronal cell death by hydrogen peroxide. J Pharmacol Sci 2006, 101: 66–76.

    Article  CAS  PubMed  Google Scholar 

  116. Jia J, Verma S, Nakayama S, Quillinan N, Grafe MR, Hurn PD, et al. Sex differences in neuroprotection provided by inhibition of TRPM2 channels following experimental stroke. J Cereb Blood Flow Metab 2011, 31: 2160–2168.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Ostapchenko VG, Chen M, Guzman MS, Xie YF, Lavine N, Fan J, et al. The transient receptor potential melastatin 2 (TRPM2) channel contributes to β-amyloid oligomer-related neurotoxicity and memory impairment. J Neurosci 2015, 35: 15157–15169.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Verma S, Quillinan N, Yang YF, Nakayama S, Cheng J, Kelley MH, et al. TRPM2 channel activation following in vitro ischemia contributes to male hippocampal cell death. Neurosci Lett 2012, 530: 41–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Nakayama S, Vest R, Traystman RJ, Herson PS. Sexually dimorphic response of TRPM2 inhibition following cardiac arrest-induced global cerebral ischemia in mice. J Mol Neurosci 2013, 51: 92–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Alim I, Teves L, Li R, Mori Y, Tymianski M. Modulation of NMDAR subunit expression by TRPM2 channels regulates neuronal vulnerability to ischemic cell death. J Neurosci 2013, 33: 17264–17277.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Ye M, Yang W, Ainscough JF, Hu XP, Li X, Sedo A, et al. TRPM2 channel deficiency prevents delayed cytosolic Zn2+ accumulation and CA1 pyramidal neuronal death after transient global ischemia. Cell Death Dis 2014, 5: e1541.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Huang S, Turlova E, Li F, Bao MH, Szeto V, Wong R, et al. Transient receptor potential melastatin 2 channels (TRPM2) mediate neonatal hypoxic-ischemic brain injury in mice. Exp Neurol 2017, 296: 32–40.

    Article  CAS  PubMed  Google Scholar 

  123. Liu HW, Gong LN, Lai K, Yu XF, Liu ZQ, Li MX, et al. Bilirubin gates the TRPM2 channel as a direct agonist to exacerbate ischemic brain damage. Neuron 2023, 111: 1609-1625.e6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Xie YF, Belrose JC, Lei G, Tymianski M, Mori Y, MacDonald JF, et al. Dependence of NMDA/GSK-3β mediated metaplasticity on TRPM2 channels at hippocampal CA3-CA1 synapses. Mol Brain 2011, 4: 44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Zong P, Feng J, Yue Z, Li Y, Wu G, Sun B, et al. Functional coupling of TRPM2 and extrasynaptic NMDARs exacerbates excitotoxicity in ischemic brain injury. Neuron 2022, 110: 1944-1958.e8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Miyanohara J, Kakae M, Nagayasu K, Nakagawa T, Mori Y, Arai K, et al. TRPM2 channel aggravates CNS inflammation and cognitive impairment via activation of microglia in chronic cerebral hypoperfusion. J Neurosci 2018, 38: 3520–3533.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Lee M, Cho T, Jantaratnotai N, Wang YT, McGeer E, McGeer PL. Depletion of GSH in glial cells induces neurotoxicity: Relevance to aging and degenerative neurological diseases. FASEB J 2010, 24: 2533–2545.

    Article  CAS  PubMed  Google Scholar 

  128. Hecquet CM, Ahmmed GU, Vogel SM, Malik AB. Role of TRPM2 channel in mediating H2O2-induced Ca2+ entry and endothelial hyperpermeability. Circ Res 2008, 102: 347–355.

    Article  CAS  PubMed  Google Scholar 

  129. Zong P, Feng J, Li CX, Jellison ER, Yue Z, Miller B, et al. Activation of endothelial TRPM2 exacerbates blood-brain barrier degradation in ischemic stroke. Cardiovasc Res 2023: cvad126.

  130. Armulik A, Genové G, Mäe M, Nisancioglu MH, Wallgard E, Niaudet C, et al. Pericytes regulate the blood-brain barrier. Nature 2010, 468: 557–561.

    Article  CAS  PubMed  Google Scholar 

  131. Jiang Q, Gao Y, Wang C, Tao R, Wu Y, Zhan K, et al. Nitration of TRPM2 as a molecular switch induces autophagy during brain pericyte injury. Antioxid Redox Signal 2017, 27: 1297–1316.

    Article  CAS  PubMed  Google Scholar 

  132. Chen ZQ, Mou RT, Feng DX, Wang Z, Chen G. The role of nitric oxide in stroke. Med Gas Res 2017, 7: 194–203.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Zhang Z, Zhang W, Jung DY, Ko HJ, Lee Y, Friedline RH, et al. TRPM2 Ca2+ channel regulates energy balance and glucose metabolism. Am J Physiol Endocrinol Metab 2012, 302: E807–E816.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Zong P, Feng J, Yue Z, Yu AS, Mori Y, Yue L. TRPM2 deficiency protects against atherosclerosis by inhibiting TRPM2-CD36 inflammatory axis in macrophages. bioRxiv 2021.07.29.454234; doi: https://doi.org/10.1101/2021.07.29.454234

  135. Beceiro S, Radin JN, Chatuvedi R, Piazuelo MB, Horvarth DJ, Cortado H, et al. TRPM2 ion channels regulate macrophage polarization and gastric inflammation during Helicobacter pylori infection. Mucosal Immunol 2017, 10: 493–507.

    Article  CAS  PubMed  Google Scholar 

  136. Knowles H, Heizer JW, Li Y, Chapman K, Ogden CA, Andreasen K, et al. Transient Receptor Potential Melastatin 2 (TRPM2) ion channel is required for innate immunity against Listeria monocytogenes. Proc Natl Acad Sci U S A 2011, 108: 11578–11583.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Kashio M, Sokabe T, Shintaku K, Uematsu T, Fukuta N, Kobayashi N, et al. Redox signal-mediated sensitization of transient receptor potential melastatin 2 (TRPM2) to temperature affects macrophage functions. Proc Natl Acad Sci U S A 2012, 109: 6745–6750.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Zou J, Ainscough JF, Yang W, Sedo A, Yu SP, Mei ZZ, et al. A differential role of macrophage TRPM2 channels in Ca2+ signaling and cell death in early responses to H2O2. Am J Physiol Cell Physiol 2013, 305: C61–C69.

    Article  CAS  PubMed  Google Scholar 

  139. Zong P, Feng J, Yue Z, Yu AS, Vacher J, Jellison ER, et al. TRPM2 deficiency in mice protects against atherosclerosis by inhibiting TRPM2-CD36 inflammatory axis in macrophages. Nat Cardiovasc Res 2022, 1: 344–360.

    Article  PubMed  PubMed Central  Google Scholar 

  140. Gelderblom M, Melzer N, Schattling B, Göb E, Hicking G, Arunachalam P, et al. Transient receptor potential melastatin subfamily member 2 cation channel regulates detrimental immune cell invasion in ischemic stroke. Stroke 2014, 45: 3395–3402.

    Article  CAS  PubMed  Google Scholar 

  141. Zhang H, Yu P, Lin H, Jin Z, Zhao S, Zhang Y, et al. The discovery of novel ACA derivatives as specific TRPM2 inhibitors that reduce ischemic injury both in vitro and in vivo. J Med Chem 2021, 64: 3976–3996.

    Article  CAS  PubMed  Google Scholar 

  142. Xu XZ, Moebius F, Gill DL, Montell C. Regulation of melastatin, a TRP-related protein, through interaction with a cytoplasmic isoform. Proc Natl Acad Sci U S A 2001, 98: 10692–10697.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Nilius B, Prenen J, Tang J, Wang C, Owsianik G, Janssens A, et al. Regulation of the Ca2+ sensitivity of the nonselective cation channel TRPM4. J Biol Chem 2005, 280: 6423–6433.

    Article  CAS  PubMed  Google Scholar 

  144. Nilius B, Mahieu F, Prenen J, Janssens A, Owsianik G, Vennekens R, et al. The Ca2+-activated cation channel TRPM4 is regulated by phosphatidylinositol 4, 5-biphosphate. EMBO J 2006, 25: 467–478.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Huang Y, Fliegert R, Guse AH, Lü W, Du J. A structural overview of the ion channels of the TRPM family. Cell Calcium 2020, 85: 102111.

    Article  CAS  PubMed  Google Scholar 

  146. Dutta Banik D, Martin LE, Freichel M, Torregrossa AM, Medler KF. TRPM4 and TRPM5 are both required for normal signaling in taste receptor cells. Proc Natl Acad Sci U S A 2018, 115: E772–E781.

    Article  PubMed  PubMed Central  Google Scholar 

  147. Mehta RI, Tosun C, Ivanova S, Tsymbalyuk N, Famakin BM, Kwon MS, et al. Sur1-Trpm4 cation channel expression in human cerebral infarcts. J Neuropathol Exp Neurol 2015, 74: 835–849.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Stokum JA, Kwon MS, Woo SK, Tsymbalyuk O, Vennekens R, Gerzanich V, et al. SUR1-TRPM4 and AQP4 form a heteromultimeric complex that amplifies ion/water osmotic coupling and drives astrocyte swelling. Glia 2018, 66: 108–125.

    Article  PubMed  Google Scholar 

  150. Stokum JA, Shim B, Negoita S, Tsymbalyuk N, Tsymbalyuk O, Ivanova S, et al. Cation flux through SUR1-TRPM4 and NCX1 in astrocyte endfeet induces water influx through AQP4 and brain swelling after ischemic stroke. Sci Signal 2023, 16: eadd6364.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Woo SK, Tsymbalyuk N, Tsymbalyuk O, Ivanova S, Gerzanich V, Simard JM. SUR1-TRPM4 channels, not KATP, mediate brain swelling following cerebral ischemia. Neurosci Lett 2020, 718: 134729.

    Article  PubMed  Google Scholar 

  152. Gerzanich V, Kwon MS, Woo SK, Ivanov A, Simard JM. SUR1-TRPM4 channel activation and phasic secretion of MMP-9 induced by tPA in brain endothelial cells. PLoS One 2018, 13: e0195526.

    Article  PubMed  PubMed Central  Google Scholar 

  153. Yan J, Bengtson CP, Buchthal B, Hagenston AM, Bading H. Coupling of NMDA receptors and TRPM4 guides discovery of unconventional neuroprotectants. Science 2020, 370: eaay3302.

    Article  CAS  PubMed  Google Scholar 

  154. Becerra A, Echeverría C, Varela D, Sarmiento D, Armisén R, Nuñez-Villena F, et al. Transient receptor potential melastatin 4 inhibition prevents lipopolysaccharide-induced endothelial cell death. Cardiovasc Res 2011, 91: 677–684.

    Article  CAS  PubMed  Google Scholar 

  155. Loh KP, Ng G, Yu CY, Fhu CK, Yu D, Vennekens R, et al. TRPM4 inhibition promotes angiogenesis after ischemic stroke. Pflugers Arch - Eur J Physiol 2014, 466: 563–576.

    Article  CAS  Google Scholar 

  156. Chen B, Ng G, Gao Y, Low SW, Sandanaraj E, Ramasamy B, et al. Non-invasive multimodality imaging directly shows TRPM4 inhibition ameliorates stroke reperfusion injury. Transl Stroke Res 2019, 10: 91–103.

    Article  CAS  PubMed  Google Scholar 

  157. Serafini N, Dahdah A, Barbet G, Demion M, Attout T, Gautier G, et al. The TRPM4 channel controls monocyte and macrophage, but not neutrophil, function for survival in sepsis. J Immunol 2012, 189: 3689–3699.

    Article  CAS  PubMed  Google Scholar 

  158. Launay P, Cheng H, Srivatsan S, Penner R, Fleig A, Kinet JP. TRPM4 regulates calcium oscillations after T cell activation. Science 2004, 306: 1374–1377.

    Article  CAS  PubMed  Google Scholar 

  159. Nadler MJ, Hermosura MC, Inabe K, Perraud AL, Zhu Q, Stokes AJ, et al. LTRPC7 is a Mg. ATP-regulated divalent cation channel required for cell viability. Nature 2001, 411: 590–595.

    Article  CAS  PubMed  Google Scholar 

  160. Runnels LW, Yue L, Clapham DE. TRP-PLIK, a bifunctional protein with kinase and ion channel activities. Science 2001, 291: 1043–1047.

    Article  CAS  PubMed  Google Scholar 

  161. Krapivinsky G, Krapivinsky L, Manasian Y, Clapham DE. The TRPM7 chanzyme is cleaved to release a chromatin-modifying kinase. Cell 2014, 157: 1061–1072.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  162. Chubanov V, Waldegger S, Schnitzler MMY, Vitzthum H, Sassen MC, Seyberth HW, et al. Disruption of TRPM6/TRPM7 complex formation by a mutation in the TRPM6 gene causes hypomagnesemia with secondary hypocalcemia. Proc Natl Acad Sci U S A 2004, 101: 2894–2899.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  163. Schmitz C, Perraud AL, Johnson CO, Inabe K, Smith MK, Penner R, et al. Regulation of vertebrate cellular Mg2+ homeostasis by TRPM7. Cell 2003, 114: 191–200.

    Article  CAS  PubMed  Google Scholar 

  164. Runnels LW, Yue L, Clapham DE. The TRPM7 channel is inactivated by PIP2 hydrolysis. Nat Cell Biol 2002, 4: 329–336.

    Article  CAS  PubMed  Google Scholar 

  165. Jiang J, Li M, Yue L. Potentiation of TRPM7 inward currents by protons. J Gen Physiol 2005, 126: 137–150.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  166. Numata T, Shimizu T, Okada Y. TRPM7 is a stretch- and swelling-activated cation channel involved in volume regulation in human epithelial cells. Am J Physiol Cell Physiol 2007, 292: C460–C467.

    Article  CAS  PubMed  Google Scholar 

  167. Oancea E, Wolfe JT, Clapham DE. Functional TRPM7 channels accumulate at the plasma membrane in response to fluid flow. Circ Res 2006, 98: 245–253.

    Article  CAS  PubMed  Google Scholar 

  168. Levine RL. Ischemia: From acidosis to oxidation. FASEB J 1993, 7: 1242–1246.

    Article  CAS  PubMed  Google Scholar 

  169. Jin J, Desai BN, Navarro B, Donovan A, Andrews NC, Clapham DE. Deletion of Trpm7 disrupts embryonic development and thymopoiesis without altering Mg2+ homeostasis. Science 2008, 322: 756–760.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Jin J, Wu LJ, Jun J, Cheng X, Xu H, Andrews NC, et al. The channel kinase, TRPM7, is required for early embryonic development. Proc Natl Acad Sci U S A 2012, 109: E225–E233.

    Article  CAS  PubMed  Google Scholar 

  171. Sah R, Mesirca P, van den Boogert M, Rosen J, Mably J, Mangoni ME, et al. Ion channel-kinase TRPM7 is required for maintaining cardiac automaticity. Proc Natl Acad Sci U S A 2013, 110: E3037–E3046.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  172. Mittermeier L, Demirkhanyan L, Stadlbauer B, Breit A, Recordati C, Hilgendorff A, et al. TRPM7 is the central gatekeeper of intestinal mineral absorption essential for postnatal survival. Proc Natl Acad Sci U S A 2019, 116: 4706–4715.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  173. Yuqiang Liu. TRPM7 is required for normal synapse density, learning, and memory at different developmental stages. Cell Rep 2018, 23: 3480–3491.

    Article  Google Scholar 

  174. Jiang ZJ, Li W, Yao LH, Saed B, Rao Y, Grewe BS, et al. TRPM7 is critical for short-term synaptic depression by regulating synaptic vesicle endocytosis. Elife 2021, 10: e66709.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  175. Abumaria N, Li W, Clarkson AN. Role of the chanzyme TRPM7 in the nervous system in health and disease. Cell Mol Life Sci 2019, 76: 3301–3310.

    Article  CAS  PubMed  Google Scholar 

  176. Lin J, Xiong ZG. TRPM7 is a unique target for therapeutic intervention of stroke. Int J Physiol Pathophysiol Pharmacol 2017, 9: 211–216.

    CAS  PubMed  PubMed Central  Google Scholar 

  177. Aarts M, Iihara K, Wei WL, Xiong ZG, Arundine M, Cerwinski W, et al. A key role for TRPM7 channels in anoxic neuronal death. Cell 2003, 115: 863–877.

    Article  CAS  PubMed  Google Scholar 

  178. Sun HS, Jackson MF, Martin LJ, Jansen K, Teves L, Cui H, et al. Suppression of hippocampal TRPM7 protein prevents delayed neuronal death in brain ischemia. Nat Neurosci 2009, 12: 1300–1307.

    Article  CAS  PubMed  Google Scholar 

  179. Zhang P, Li W, Liu Y, Gao Y, Abumaria N. Neuroprotective effects of TRPM7 deletion in parvalbumin GABAergic vs. glutamatergic neurons following ischemia. Cells 2022, 11: 1178.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  180. Inoue K, Branigan D, Xiong ZG. Zinc-induced neurotoxicity mediated by transient receptor potential melastatin 7 channels. J Biol Chem 2010, 285: 7430–7439.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  181. Morris DR, Levenson CW. Neurotoxicity of Zinc. Advances in Neurobiology. Cham: Springer International Publishing, 2017: 303–312.

  182. Wu W, Wang X, Liao L, Chen J, Wang Y, Yao M, et al. The TRPM7 channel reprograms cellular glycolysis to drive tumorigenesis and angiogenesis. Cell Death Dis 2023, 14: 183.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  183. Paravicini TM, Yogi A, Mazur A, Touyz RM. Dysregulation of vascular TRPM7 and annexin-1 is associated with endothelial dysfunction in inherited hypomagnesemia. Hypertension 2009, 53: 423–429.

    Article  CAS  PubMed  Google Scholar 

  184. Cesare P, McNaughton P. A novel heat-activated current in nociceptive neurons and its sensitization by bradykinin. Proc Natl Acad Sci U S A 1996, 93: 15435–15439.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  185. Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D. The capsaicin receptor: A heat-activated ion channel in the pain pathway. Nature 1997, 389: 816–824.

    Article  CAS  PubMed  Google Scholar 

  186. Nilius B, Vennekens R, Prenen J, Hoenderop JG, Droogmans G, Bindels RJ. The single pore residue Asp542 determines Ca2+ permeation and Mg2+ block of the epithelial Ca2+ channel. J Biol Chem 2001, 276: 1020–1025.

    Article  CAS  PubMed  Google Scholar 

  187. Saotome K, Singh AK, Yelshanskaya MV, Sobolevsky AI. Crystal structure of the epithelial calcium channel TRPV6. Nature 2016, 534: 506–511.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  188. Chung MK, Güler AD, Caterina MJ. TRPV1 shows dynamic ionic selectivity during agonist stimulation. Nat Neurosci 2008, 11: 555–564.

    Article  CAS  PubMed  Google Scholar 

  189. Rosenbaum T, Islas LD. Molecular physiology of TRPV channels: Controversies and future challenges. Annu Rev Physiol 2023, 85: 293–316.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  191. Doerner JF, Hatt H, Ramsey IS. Voltage- and temperature-dependent activation of TRPV3 channels is potentiated by receptor-mediated PI(4, 5)P2 hydrolysis. J Gen Physiol 2011, 137: 271–288.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  192. Wang B, Wu L, Chen J, Dong L, Chen C, Wen Z, et al. Metabolism pathways of arachidonic acids: Mechanisms and potential therapeutic targets. Signal Transduct Target Ther 2021, 6: 94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  193. Sun X, Zakharian E. Regulation of the temperature-dependent activation of transient receptor potential vanilloid 1 (TRPV1) by phospholipids in planar lipid bilayers. J Biol Chem 2015, 290: 4741–4747.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  194. Marrone MC, Morabito A, Giustizieri M, Chiurchiù V, Leuti A, Mattioli M, et al. TRPV1 channels are critical brain inflammation detectors and neuropathic pain biomarkers in mice. Nat Commun 2017, 8: 15292.

    Article  PubMed  PubMed Central  Google Scholar 

  195. Menigoz A, Boudes M. The expression pattern of TRPV1 in brain. J Neurosci 2011, 31: 13025–13027.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  196. Shuba YM. Beyond neuronal heat sensing: Diversity of TRPV1 heat-capsaicin receptor-channel functions. Front Cell Neurosci 2020, 14: 612480.

    Article  CAS  PubMed  Google Scholar 

  197. Molinas AJR, Desmoulins LD, Hamling BV, Butcher SM, Anwar IJ, Miyata K, et al. Interaction between TRPV1-expressing neurons in the hypothalamus. J Neurophysiol 2019, 121: 140–151.

    Article  CAS  PubMed  Google Scholar 

  198. Balleza-Tapia H, Crux S, Andrade-Talavera Y, Dolz-Gaiton P, Papadia D, Chen G, et al. TrpV1 receptor activation rescues neuronal function and network gamma oscillations from Aβ-induced impairment in mouse hippocampus in vitro. Elife 2018, 7: e37703.

    Article  PubMed  PubMed Central  Google Scholar 

  199. Hurtado-Zavala JI, Ramachandran B, Ahmed S, Halder R, Bolleyer C, Awasthi A, et al. TRPV1 regulates excitatory innervation of OLM neurons in the hippocampus. Nat Commun 2017, 8: 15878.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  200. Garami A, Pakai E, Oliveira DL, Steiner AA, Wanner SP, Almeida MC, et al. Thermoregulatory phenotype of the Trpv1 knockout mouse: Thermoeffector dysbalance with hyperkinesis. J Neurosci 2011, 31: 1721–1733.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  201. Aneiros E, Cao L, Papakosta M, Stevens EB, Phillips S, Grimm C. The biophysical and molecular basis of TRPV1 proton gating. EMBO J 2011, 30: 994–1002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  202. Yenari MA, Hemmen TM. Therapeutic hypothermia for brain ischemia: Where have we come and where do we go? Stroke 2010, 41: S72–S74.

    Article  PubMed  PubMed Central  Google Scholar 

  203. Gavva NR, Bannon AW, Surapaneni S, Hovland DN Jr, Lehto SG, Gore A, et al. The vanilloid receptor TRPV1 is tonically Activated In Vivo and involved in body temperature regulation. J Neurosci 2007, 27: 3366–3374.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  204. Yue WWS, Yuan L, Braz JM, Basbaum AI, Julius D. TRPV1 drugs alter core body temperature via central projections of primary afferent sensory neurons. Elife 2022, 11: e80139.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  205. Fosgerau K, Weber UJ, Gotfredsen JW, Jayatissa M, Buus C, Kristensen NB, et al. Drug-induced mild therapeutic hypothermia obtained by administration of a transient receptor potential vanilloid type 1 agonist. BMC Cardiovasc Disord 2010, 10: 51.

    Article  PubMed  PubMed Central  Google Scholar 

  206. Cao Z, Balasubramanian A, Marrelli SP. Pharmacologically induced hypothermia via TRPV1 channel agonism provides neuroprotection following ischemic stroke when initiated 90 Min after reperfusion. Am J Physiol Regul Integr Comp Physiol 2014, 306: R149–R156.

    Article  CAS  PubMed  Google Scholar 

  207. Muzzi M, Felici R, Cavone L, Gerace E, Minassi A, Appendino G, et al. Ischemic neuroprotection by TRPV1 receptor-induced hypothermia. J Cereb Blood Flow Metab 2012, 32: 978–982.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  208. Cao Z, Balasubramanian A, Pedersen SE, Romero J, Pautler RG, Marrelli SP. TRPV1-mediated pharmacological hypothermia promotes improved functional recovery following ischemic stroke. Sci Rep 2017, 7: 17685.

    Article  PubMed  PubMed Central  Google Scholar 

  209. Huang M, Cheng G, Tan H, Qin R, Zou Y, Wang Y, et al. Capsaicin protects cortical neurons against ischemia/reperfusion injury via down-regulating NMDA receptors. Exp Neurol 2017, 295: 66–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  210. Miyanohara J, Shirakawa H, Sanpei K, Nakagawa T, Kaneko S. A pathophysiological role of TRPV1 in ischemic injury after transient focal cerebral ischemia in mice. Biochem Biophys Res Commun 2015, 467: 478–483.

    Article  CAS  PubMed  Google Scholar 

  211. Hakimizadeh E, Shamsizadeh A, Roohbakhsh A, Arababadi MK, Hajizadeh MR, Shariati M, et al. Inhibition of transient receptor potential vanilloid-1 confers neuroprotection, reduces tumor necrosis factor-alpha, and increases IL-10 in a rat stroke model. Fundam Clin Pharmacol 2017, 31: 420–428.

    Article  CAS  PubMed  Google Scholar 

  212. Yang XL, Wang X, Shao L, Jiang GT, Min JW, Mei XY, et al. TRPV1 mediates astrocyte activation and interleukin-1β release induced by hypoxic ischemia (HI). J Neuroinflammation 2019, 16: 114.

    Article  PubMed  PubMed Central  Google Scholar 

  213. Zhang Y, Hou B, Liang P, Lu X, Wu Y, Zhang X, et al. TRPV1 channel mediates NLRP3 inflammasome-dependent neuroinflammation in microglia. Cell Death Dis 2021, 12: 1159.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  214. Wang C, Huang W, Lu J, Chen H, Yu Z. TRPV1-mediated microglial autophagy attenuates alzheimer’s disease-associated pathology and cognitive decline. Front Pharmacol 2021, 12: 763866.

    Article  CAS  PubMed  Google Scholar 

  215. Zhu R, Luo Y, Li S, Wang Z. The role of microglial autophagy in Parkinson’s disease. Front Aging Neurosci 2022, 14: 1039780.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  216. Ching LC, Chen CY, Su KH, Hou HH, Shyue SK, Kou YR, et al. Implication of AMP-activated protein kinase in transient receptor potential vanilloid type 1-mediated activation of endothelial nitric oxide synthase. Mol Med 2012, 18: 805–815.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  217. Ching LC, Kou YR, Shyue SK, Su KH, Wei J, Cheng LC, et al. Molecular mechanisms of activation of endothelial nitric oxide synthase mediated by transient receptor potential vanilloid type 1. Cardiovasc Res 2011, 91: 492–501.

    Article  CAS  PubMed  Google Scholar 

  218. Adamczak J, Hoehn M. Poststroke angiogenesis, con: Dark side of angiogenesis. Stroke 2015, 46: e103–e104.

    Article  PubMed  Google Scholar 

  219. Zhu J, Song W, Li L, Fan X. Endothelial nitric oxide synthase: A potential therapeutic target for cerebrovascular diseases. Mol Brain 2016, 9: 30.

    Article  PubMed  PubMed Central  Google Scholar 

  220. Lv Z, Xu X, Sun Z, Yang YX, Guo H, Li J, et al. TRPV1 alleviates osteoarthritis by inhibiting M1 macrophage polarization via Ca2+/CaMKII/Nrf2 signaling pathway. Cell Death Dis 2021, 12: 504.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  221. Pumroy RA, Protopopova AD, Fricke TC, Lange IU, Haug FM, Nguyen PT, et al. Structural insights into TRPV2 activation by small molecules. Nat Commun 2022, 13: 2334.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  222. Katanosaka K, Takatsu S, Mizumura K, Naruse K, Katanosaka Y. TRPV2 is required for mechanical nociception and the stretch-evoked response of primary sensory neurons. Sci Rep 2018, 8: 16782.

    Article  PubMed  PubMed Central  Google Scholar 

  223. Nedungadi TP, Dutta M, Bathina CS, Caterina MJ, Cunningham JT. Expression and distribution of TRPV2 in rat brain. Exp Neurol 2012, 237: 223–237.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  224. Shibasaki K, Murayama N, Ono K, Ishizaki Y, Tominaga M. TRPV2 enhances axon outgrowth through its activation by membrane stretch in developing sensory and motor neurons. J Neurosci 2010, 30: 4601–4612.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  225. Cohen MR, Johnson WM, Pilat JM, Kiselar J, DeFrancesco-Lisowitz A, Zigmond RE, et al. Nerve growth factor regulates transient receptor potential vanilloid 2 via extracellular signal-regulated kinase signaling to enhance neurite outgrowth in developing neurons. Mol Cell Biol 2015, 35: 4238–4252.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  226. Park U, Vastani N, Guan Y, Raja SN, Koltzenburg M, Caterina MJ. TRP vanilloid 2 knock-out mice are susceptible to perinatal lethality but display normal thermal and mechanical nociception. J Neurosci 2011, 31: 11425–11436.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  227. Zhang H, Xiao J, Hu Z, Xie M, Wang W, He D. Blocking transient receptor potential vanilloid 2 channel in astrocytes enhances astrocyte-mediated neuroprotection after oxygen-glucose deprivation and reoxygenation. Eur J Neurosci 2016, 44: 2493–2503.

    Article  PubMed  Google Scholar 

  228. Choi SH, Mou Y, Silva AC. Cannabis and cannabinoid biology in stroke. Stroke 2019, 50: 2640–2645.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  229. Hassan S, Eldeeb K, Millns PJ, Bennett AJ, Alexander SP, Kendall DA. Cannabidiol enhances microglial phagocytosis via transient receptor potential (TRP) channel activation. Br J Pharmacol 2014, 171: 2426–2439.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  230. Luo H, Rossi E, Saubamea B, Chasseigneaux S, Cochois V, Choublier N, et al. Cannabidiol increases proliferation, migration, tubulogenesis, and integrity of human brain endothelial cells through TRPV2 activation. Mol Pharm 2019, 16: 1312–1326.

    Article  CAS  PubMed  Google Scholar 

  231. Peng S, Poole DP, Veldhuis NA. Mini-review: Dissecting receptor-mediated stimulation of TRPV4 in nociceptive and inflammatory pathways. Neurosci Lett 2022, 770: 136377.

    Article  CAS  PubMed  Google Scholar 

  232. Peier AM, Reeve AJ, Andersson DA, Moqrich A, Earley TJ, Hergarden AC, et al. A heat-sensitive TRP channel expressed in keratinocytes. Science 2002, 296: 2046–2049.

    Article  CAS  PubMed  Google Scholar 

  233. Smith GD, Gunthorpe MJ, Kelsell RE, Hayes PD, Reilly P, Facer P, et al. TRPV3 is a temperature-sensitive vanilloid receptor-like protein. Nature 2002, 418: 186–190.

    Article  CAS  PubMed  Google Scholar 

  234. Xu H, Ramsey IS, Kotecha SA, Moran MM, Chong JA, Lawson D, et al. TRPV3 is a calcium-permeable temperature-sensitive cation channel. Nature 2002, 418: 181–186.

    Article  CAS  PubMed  Google Scholar 

  235. Cao X, Yang F, Zheng J, Wang K. Intracellular proton-mediated activation of TRPV3 channels accounts for the exfoliation effect of α-hydroxyl acids on keratinocytes. J Biol Chem 2012, 287: 25905–25916.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  236. Hu HZ, Xiao R, Wang C, Gao N, Colton CK, Wood JD, et al. Potentiation of TRPV3 channel function by unsaturated fatty acids. J Cell Physiol 2006, 208: 201–212.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  237. Xu H, Delling M, Jun JC, Clapham DE. Oregano, thyme and clove-derived flavors and skin sensitizers activate specific TRP channels. Nat Neurosci 2006, 9: 628–635.

    Article  CAS  PubMed  Google Scholar 

  238. Ho JC, Lee CH. TRP channels in skin: From physiological implications to clinical significances. Biophysics (Nagoya-Shi) 2015, 11: 17–24.

    Article  CAS  PubMed  Google Scholar 

  239. Danso-Abeam D, Zhang J, Dooley J, Staats KA, van Eyck L, van Brussel T, et al. Olmsted syndrome: Exploration of the immunological phenotype. Orphanet J Rare Dis 2013, 8: 79.

    Article  PubMed  PubMed Central  Google Scholar 

  240. Duchatelet S, Guibbal L, de Veer S, Fraitag S, Nitschké P, Zarhrate M, et al. Olmsted syndrome with erythromelalgia caused by recessive transient receptor potential vanilloid 3 mutations. Br J Dermatol 2014, 171: 675–678.

    Article  CAS  PubMed  Google Scholar 

  241. Duchatelet S, Pruvost S, de Veer S, Fraitag S, Nitschké P, Bole-Feysot C, et al. A new TRPV3 missense mutation in a patient with Olmsted syndrome and erythromelalgia. JAMA Dermatol 2014, 150: 303–306.

    Article  PubMed  Google Scholar 

  242. Eytan O, Fuchs-Telem D, Mevorach B, Indelman M, Bergman R, Sarig O, et al. Olmsted syndrome caused by a homozygous recessive mutation in TRPV3. J Invest Dermatol 2014, 134: 1752–1754.

    Article  CAS  PubMed  Google Scholar 

  243. Nilius B, Bíró T, Owsianik G. TRPV3: Time to decipher a poorly understood family member! J Physiol 2014, 592: 295–304.

    Article  CAS  PubMed  Google Scholar 

  244. Ni C, Yan M, Zhang J, Cheng R, Liang J, Deng D, et al. A novel mutation in TRPV3 gene causes atypical familial Olmsted syndrome. Sci Rep 2016, 6: 21815.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  245. Greco C, Leclerc-Mercier S, Chaumon S, Doz F, Hadj-Rabia S, Molina T, et al. Use of epidermal growth factor receptor inhibitor erlotinib to treat palmoplantar keratoderma in patients with Olmsted syndrome caused by TRPV3 mutations. JAMA Dermatol 2020, 156: 191–195.

    Article  PubMed  PubMed Central  Google Scholar 

  246. Moussaieff A, Yu J, Zhu H, Gattoni-Celli S, Shohami E, Kindy MS. Protective effects of incensole acetate on cerebral ischemic injury. Brain Res 2012, 1443: 89–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  247. Chen X, Zhang J, Wang K. Inhibition of intracellular proton-sensitive Ca2+-permeable TRPV3 channels protects against ischemic brain injury. Acta Pharm Sin B 2022, 12: 2330–2347.

    Article  PubMed  PubMed Central  Google Scholar 

  248. Toft-Bertelsen TL, MacAulay N. TRPing to the point of clarity: Understanding the function of the complex TRPV4 ion channel. Cells 2021, 10: 165.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  249. Willette RN, Bao W, Nerurkar S, Yue TL, Doe CP, Stankus G, et al. Systemic activation of the transient receptor potential vanilloid subtype 4 channel causes endothelial failure and circulatory collapse: Part 2. J Pharmacol Exp Ther 2008, 326: 443–452.

    Article  CAS  PubMed  Google Scholar 

  250. Malczyk M, Veith C, Fuchs B, Hofmann K, Storch U, Schermuly RT, et al. Classical transient receptor potential channel 1 in hypoxia-induced pulmonary hypertension. Am J Respir Crit Care Med 2013, 188: 1451–1459.

    Article  CAS  PubMed  Google Scholar 

  251. Yang XR, Lin AH, Hughes JM, Flavahan NA, Cao YN, Liedtke W, et al. Upregulation of osmo-mechanosensitive TRPV4 channel facilitates chronic hypoxia-induced myogenic tone and pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 2012, 302: L555–L568.

    Article  CAS  PubMed  Google Scholar 

  252. Kumar H, Lee SH, Kim KT, Zeng X, Han I. TRPV4: A sensor for homeostasis and pathological events in the CNS. Mol Neurobiol 2018, 55: 8695–8708.

    Article  CAS  PubMed  Google Scholar 

  253. Toft-Bertelsen TL, MacAulay N. TRPing on cell swelling - TRPV4 senses it. Front Immunol 2021, 12: 730982.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  254. Rungta RL, Choi HB, Tyson JR, Malik A, Dissing-Olesen L, Lin PJC, et al. The cellular mechanisms of neuronal swelling underlying cytotoxic edema. Cell 2015, 161: 610–621.

    Article  CAS  PubMed  Google Scholar 

  255. Fricker M, Tolkovsky AM, Borutaite V, Coleman M, Brown GC. Neuronal cell death. Physiol Rev 2018, 98: 813–880.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  256. Li L, Qu W, Zhou L, Lu Z, Jie P, Chen L, et al. Activation of transient receptor potential vanilloid 4 increases NMDA-activated current in hippocampal pyramidal neurons. Front Cell Neurosci 2013, 7: 17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  257. Hong Z, Tian Y, Qi M, Li Y, Du Y, Chen L, et al. Transient receptor potential vanilloid 4 inhibits γ-aminobutyric acid-activated current in hippocampal pyramidal neurons. Front Mol Neurosci 2016, 9: 77.

    Article  PubMed  PubMed Central  Google Scholar 

  258. Özşimşek A, Nazıroğlu M. The involvement of TRPV4 on the hypoxia-induced oxidative neurotoxicity and apoptosis in a neuronal cell line: Protective role of melatonin. Neurotoxicology 2021, 87: 136–148.

    Article  PubMed  Google Scholar 

  259. Shibasaki K, Ikenaka K, Tamalu F, Tominaga M, Ishizaki Y. A novel subtype of astrocytes expressing TRPV4 (transient receptor potential vanilloid 4) regulates neuronal excitability via release of gliotransmitters. J Biol Chem 2014, 289: 14470–14480.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  260. Benfenati V, Amiry-Moghaddam M, Caprini M, Mylonakou MN, Rapisarda C, Ottersen OP, et al. Expression and functional characterization of transient receptor potential vanilloid-related channel 4 (TRPV4) in rat cortical astrocytes. Neuroscience 2007, 148: 876–892.

    Article  CAS  PubMed  Google Scholar 

  261. Butenko O, Dzamba D, Benesova J, Honsa P, Benfenati V, Rusnakova V, et al. The increased activity of TRPV4 channel in the astrocytes of the adult rat hippocampus after cerebral hypoxia/ischemia. PLoS One 2012, 7: e39959.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  262. Hu X, Du L, Liu S, Lan Z, Zang K, Feng J, et al. A TRPV4-dependent neuroimmune axis in the spinal cord promotes neuropathic pain. J Clin Invest 2023, 133: e161507.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  263. Nishimoto R, Derouiche S, Eto K, Deveci A, Kashio M, Kimori Y, et al. Thermosensitive TRPV4 channels mediate temperature-dependent microglia movement. Proc Natl Acad Sci U S A 2021, 118: e2012894118.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  264. Beeken J, Mertens M, Stas N, Kessels S, Aerts L, Janssen B, et al. Acute inhibition of transient receptor potential vanilloid-type 4 cation channel halts cytoskeletal dynamism in microglia. Glia 2022, 70: 2157–2168.

    Article  CAS  PubMed  Google Scholar 

  265. Dutta B, Arya RK, Goswami R, Alharbi MO, Sharma S, Rahaman SO. Role of macrophage TRPV4 in inflammation. Lab Invest 2020, 100: 178–185.

    Article  CAS  PubMed  Google Scholar 

  266. Luo J, Qian A, Oetjen LK, Yu W, Yang P, Feng J, et al. TRPV4 channel signaling in macrophages promotes gastrointestinal motility via direct effects on smooth muscle cells. Immunity 2018, 49: 107-119.e4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  267. Yin J, Michalick L, Tang C, Tabuchi A, Goldenberg N, Dan Q, et al. Role of transient receptor potential vanilloid 4 in neutrophil activation and acute lung injury. Am J Respir Cell Mol Biol 2016, 54: 370–383.

    Article  CAS  PubMed  Google Scholar 

  268. Kumar H, Lim CS, Choi H, Joshi HP, Kim KT, Kim YH, et al. Elevated TRPV4 levels contribute to endothelial damage and scarring in experimental spinal cord injury. J Neurosci 2020, 40: 1943–1955.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This review was partially supported by the National Institute of Health (R01-HL143750 and R01NS131661) and American Heart Association (19TPA34890022) to LY, and the Connecticut Institute for the Brain and Cognitive Sciences Seed Grant (402194) to PZ.

Author information

Author notes

  1. Mara Cicchetti

    Present address: Department of Neuroscience, University of Pittsburgh, 4200 Fifth Ave, Pittsburgh, PA, 15260, USA

Authors and Affiliations

  1. Department of Cell Biology, Calhoun Cardiology Center, School of Medicine (UConn Health), University of Connecticut, Farmington, CT, 06030, USA

    Pengyu Zong, Cindy X. Li, Jianlin Feng, Mara Cicchetti & Lixia Yue

  2. Institute for the Brain and Cognitive Sciences, University of Connecticut, 337 Mansfield Road, Unit 1272, Storrs, CT, 06269, USA

    Pengyu Zong

Authors
  1. Pengyu Zong
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Cindy X. Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jianlin Feng
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mara Cicchetti
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lixia Yue
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Pengyu Zong or Lixia Yue.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zong, P., Li, C.X., Feng, J. et al. TRP Channels in Stroke. Neurosci. Bull. (2023). https://doi.org/10.1007/s12264-023-01151-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12264-023-01151-5

Keywords

Search

Navigation