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TRPM2

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Immunopharmacology Ligand  Target has curated data in GtoImmuPdb

Target id: 494

Nomenclature: TRPM2

Family: Transient Receptor Potential channels (TRP)

Contents:

Gene and Protein Information Click here for help
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 6 1 1503 21q22.3 TRPM2 transient receptor potential cation channel subfamily M member 2 35,44,47,51,60
Mouse 6 1 1506 10 39.72 cM Trpm2 transient receptor potential cation channel, subfamily M, member 2 15
Rat 6 1 1508 20p12 Trpm2 transient receptor potential cation channel, subfamily M, member 2 23
Previous and Unofficial Names Click here for help
EREG1 | KNP3 | LTRPC2 | TRPC7 | transient receptor potential melastatin family 2 | transient receptor potential cation channel
Database Links Click here for help
Alphafold O94759 (Hs), Q91YD4 (Mm)
ChEMBL Target CHEMBL1250402 (Hs)
Ensembl Gene ENSG00000142185 (Hs), ENSMUSG00000009292 (Mm), ENSRNOG00000001216 (Rn)
Entrez Gene 7226 (Hs), 28240 (Mm), 294329 (Rn)
Human Protein Atlas ENSG00000142185 (Hs)
KEGG Gene hsa:7226 (Hs), mmu:28240 (Mm), rno:294329 (Rn)
OMIM 603749 (Hs)
Pharos O94759 (Hs)
RefSeq Nucleotide NM_003307 (Hs), NM_138301 (Mm), NM_001011559 (Rn)
RefSeq Protein NP_003298 (Hs), NP_612174 (Mm), NP_001011559 (Rn)
UniProtKB O94759 (Hs), Q91YD4 (Mm)
Wikipedia TRPM2 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Human TRPM2 ion channel in a calcium- and ADPR-bound state
PDB Id:  6MJ2
Resolution:  6.36Å
Species:  Human
References:  63
Image of receptor 3D structure from RCSB PDB
Description:  Human TRPM2 ion channel in apo state
PDB Id:  6MIX
Resolution:  3.6Å
Species:  Human
References:  63
Associated Proteins Click here for help
Heteromeric Pore-forming Subunits
Name References
Not determined
Auxiliary Subunits
Name References
Not determined
Other Associated Proteins
Name References
ADPRibase 47,51
calmodulin 57
Sir2 14
EFHC1 29
ubiquitin 30,62
Functional Characteristics Click here for help
γ = 52-60 pS at negative potentials, 76 pS at positive potentials; conducts mono- and di-valent cations non-selectively (PCa/PNa = 0.6-0.7); non-rectifying; inactivation at negative potentials; activated by oxidative stress probably via PARP-1, PARP inhibitors reduce activation by oxidative stress, activation inhibited by suppression of APDR formation by glycohydrolase inhibitors.
Ion Selectivity and Conductance Click here for help
Species:  Human
Rank order:  Na+ > Ca2+ > Mg2+ > Cs+ [60.0 - 80.0 pS]
References:  17,47,51,55
Ion Selectivity and Conductance Comments
Ranking shown is for 20°C. At >35°C, PCa:PNa ≈ 6.
Voltage Dependence Comments
Voltage independent.
Chemical activators (Human)
Agents producing reactive oxygen (e.g. H2O2) and nitrogen (e.g. GEA 3162) species
Physical activators (Human)
Heat ~ 35°C

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Activators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Holding voltage (mV) Reference
NAD Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Hs Agonist - - 3x10-4 - 1x10-3 -60.0 15,17,51,55
⤷ Conc range: 3x10-4 - 1x10-3 M [15,17,51,55]
Holding voltage: -60.0 mV
H2O2 Ligand is endogenous in the given species Hs Agonist - - 5x10-7 - 5x10-5 Physiological 10,15,33,53,64
⤷ Conc range: 5x10-7 - 5x10-5 M [10,15,33,53,64]
Holding voltage: Physiological
arachidonic acid Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Hs Potentiation - - 1x10-5 - 3x10-5 Physiological 15
⤷ Conc range: 1x10-5 - 3x10-5 M [15]
Holding voltage: Physiological
OAADPR Small molecule or natural product Hs Activation 4.0 pKd - -100.0 14
⤷ pKd 4.0 (Kd 1x10-4 M) [14]
Holding voltage: -100.0 mV
intracellular cADPR Small molecule or natural product Ligand is endogenous in the given species Hs Agonist 5.0 pEC50 - -80.0 – -60.0 3,31,55
⤷ pEC50 5.0 (EC50 1x10-5 M) [3,31,55]
Holding voltage: -80.0 – -60.0 mV
intracellular ADP ribose Small molecule or natural product Ligand is endogenous in the given species Hs Agonist 3.9 – 4.4 pEC50 - -80.0 47
⤷ pEC50 3.9 – 4.4 (EC50 1.26x10-4 – 3.98x10-5 M) [47]
Holding voltage: -80.0 mV
NAADP Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Hs Agonist 3.1 pEC50 - -80.0 3
⤷ pEC50 3.1 [3]
Holding voltage: -80.0 mV
intracellular Ca2+ Click here for species-specific activity table Ligand is endogenous in the given species Hs - - - - -
⤷ perhaps via calmodulin
membrane PIP2 Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Hs Activation - - - - 59
⤷ [59]
GEA 3162 Small molecule or natural product Hs - - - - -
⤷
Activator Comments
Activation of TRPM2 is regulated by [Ca2+]i. Elevated Ca2+ levels, probably via calmodulin, sensitise TRPM2 to activation by ADPR [40,57]. Heat potentiates TRPM2 activation [55]. ADP ribose, NAD, NAADP, and OAADPR might directly bind and activate TRPM2, while H2O2 and cADPR indirectly activate TRPM2 through ADP ribose [58]. Activation by oxidative stress is probably mediated by PARP-1. PARP inhibitors (SB750139>PJ34>DPQ) decrease oxidative stress-mediated activation of TRPM2 [10,68]. Catalase [20], dimethylthiourea [53] and mannitol [64] all inhibit oxidative stress-mediated TRPM2 activation.
Gating Inhibitor Comments
Glycohydrase inhibitors inhibit endogenous ADPR formation and reduce TRPM2 activation [13]. Short splice variant TRPM2-S (846 aa) inhibits activation of the long splice variant [73]. TRPM2 is inhibited by AMP (IC50=70µM), which competes with ADP ribose for Nudix domain [31,58]. Extracellular or intracellular acidosis inhibits TRPM2; the mechanism is that the extracellular protons compete with Na+ and Ca2+ for channel permeation while intracellular protons antagonize intracellular Ca2+ binding [9,54,70]. Zinc also inactivates TRPM2 and residues in the outer pore (Lys952 and Asp1002) are critical determinants of the inactivation [69].

The GY motif in the TRPM2 selective filter is essential for channel inactivation [59].
Channel Blockers
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Holding voltage (mV) Reference
flufenamic acid Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Antagonist - - 5x10-5 - 1x10-3 -60.0 – -50.0 21,56
⤷ Conc range: 5x10-5 - 1x10-3 M [21,56]
Holding voltage: -60.0 – -50.0 mV
clotrimazole Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist - - 3x10-6 - 3x10-5 -60.0 – -15.0 22
⤷ Conc range: 3x10-6 - 3x10-5 M [22]
Holding voltage: -60.0 – -15.0 mV
econazole Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist - - 3x10-6 - 3x10-5 -60.0 – -15.0 22
⤷ Conc range: 3x10-6 - 3x10-5 M [22]
Holding voltage: -60.0 – -15.0 mV
miconazole Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist - - 1x10-5 -60.0 56
⤷ Conc range: 1x10-5 M [56]
Holding voltage: -60.0 mV
tatM2NX Peptide Hs Antagonist 6.4 pIC50 - - 7
⤷ pIC50 6.4 (IC50 3.96x10-7 M) [7]
Description: Inhibition of channel activity in HEK293 cells expressing human TRPM2.
2-APB Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 6.1 pIC50 - -60.0 56
⤷ pIC50 6.1 (IC50 8.2x10-7 M) [56]
Holding voltage: -60.0 mV
Zn2+ Click here for species-specific activity table Ligand is endogenous in the given species Hs - 6.0 pIC50 - -
⤷ pIC50 6.0 (IC50 1x10-6 M)
ACAA Small molecule or natural product Click here for species-specific activity table Hs Antagonist 5.8 pIC50 - Physiological 32
⤷ pIC50 5.8 (IC50 1.7x10-6 M) [32]
Holding voltage: Physiological
extracellular H+ Click here for species-specific activity table Ligand is endogenous in the given species Hs - - - - -
⤷
Channel Blocker Comments
Cysteine pore residues (Cys996, Cys1008) are essential for pore functions, mutations of these residues lead to dysfunctional channels [42]. Exceptionally amongst TRP channels, there is no pore block by lanthanides and heavy metal ions [33].
Immunopharmacology Comments
Expressed on human T cells, mouse dendritic cells, human and mouse neutrophils and monocytes/macrophages, and mouse mast cells [46].
Cell Type Associations
Immuno Cell Type:  Macrophages & monocytes
Cell Ontology Term:   macrophage (CL:0000235)
Comment:  TRPM2 on macrophages modulates ROS production and inflammation (including cytokine production and inflammasome activation).
References:  8,61
Immuno Cell Type:  T cells
Comment:  TRPM2 activity is involved in T cell activation and cytokine production.
References:  43
Immuno Process Associations
Immuno Process:  Inflammation
Immuno Process:  Immune system development
Immuno Process:  Chemotaxis & migration
Immuno Process:  Cellular signalling
Tissue Distribution Click here for help
Brain (cerebellum, cortex, medulla, temporal lobe, occipital lobe, frontal lobe, putamen, caudate, amygdala, hippocampus, striatum), spinal cord, bone marrow, spleen, heart, lung, eye, neutrophils, leukocytes, pancreatic β-cells.
Species:  Human
Technique:  RT-PCR, western blot, northern blot, immunocytochemistry
References:  17,41,48,55,73
Immune cells: neutrophils, monocytes, macrophages, lymphocytes (Note that TRPM2 expression in these cell types is also reported in rat and mouse).
Species:  Human
Technique:  RT-PCR, western blot, immunocytochemistry
References:  24,26,39,43,50,65,67
Pancreatic β-cells (Note that TRPM2 expression in these cells is also reported in rat and mouse).
Species:  Human
Technique:  Western blot, immunocytochemistry
References:  2,38,55
Brain/spinal cord microglia (Note that TRPM2 is also expressed in these tissues in rat).
Species:  Mouse
Technique:  In situ hybridization, RT-PCR
References:  12,16,33
Hippocampal neurons
Species:  Mouse
Technique:  In situ hybridization, western blot, immunocytochemistry
References:  45
Brain (hippocampus, cerebellum), vascular endothelium, thymocytes, pancreatic β-cells.
Species:  Mouse
Technique:  RT-PCR, western blot
References:  25,55,60,71
Dopaminergic neurons
Species:  Rat
Technique:  RT-PCR, immunohistochemistry, patch-clamp recordings, Ca2+ imaging
References:  6
Striatal neurones.
Species:  Rat
Technique:  RT-PCR
References:  23,53
Functional Assays Click here for help
Patch clamp (whole-cell and single-channel recordings), Ca2+ imaging.
Species:  Human
Tissue:  HEK 293 cells, neutrophil granulocytes.
Response measured:  Ca2+ current.
References:  17,47
Patch clamp (whole-cell and single-channel recordings), Ca2+ imaging.
Species:  Mouse
Tissue:  Thymocytes.
Response measured:  Ca2+ current.
References:  25
Patch clamp (whole-cell and single-channel recordings), Ca2+ imaging.
Species:  Rat
Tissue:  Striatal neurones.
Response measured:  Ca2+ current.
References:  23,53
Patch clamp (whole-cell and single-channel recordings), Ca2+ imaging.
Species:  Mouse
Tissue:  Hippocampal neurons
Response measured:  TRPM2-mediated whole-cell current
References:  4,45
Patch clamp (whole-cell and single-channel recordings), Ca2+ imaging.
Species:  Rat
Tissue:  Microglia
Response measured:  TRPM2-mediated whole-cell current and Ca2+ elevation
References:  12,33
Patch clamp (whole-cell and single-channel recordings), Ca2+ imaging (Note that these results are also reported in mouse)
Species:  Human
Tissue:  Neutrophils
Response measured:  TRPM2-mediated Ca2+ elevation and current
References:  24,37
Patch clamp (whole-cell and single-channel recordings), Ca2+ imaging (Note that these results are also reported in mouse and rat)
Species:  Human
Tissue:  Pancreatic β-cells
Response measured:  TRPM2-mediated current and Ca2+ elevation
References:  2,38,55
Patch clamp (whole-cell and single-channel recordings), Ca2+ imaging
Species:  Human
Tissue:  B cells
Response measured:  TRPM2-mediated Ca2+ elevation
References:  50
Patch clamp (whole-cell and single-channel recordings), Ca2+ imaging
Species:  Human
Tissue:  T cells
Response measured:  TRPM2-mediated current and Ca2+ elevation
References:  3,39
Patch clamp (whole-cell and single-channel recordings), Ca2+ imaging
Species:  Mouse
Tissue:  Macrophages
Response measured:  TRPM2-mediated whole-cell current and Ca2+ elevation
References:  8,28
Patch clamp (whole-cell and single-channel recordings), Ca2+ imaging (Note that these results are also reported in mouse)
Species:  Human
Tissue:  Monocytes
Response measured:  TRPM2-mediated whole-cell current and Ca2+ elevation
References:  65,67
Patch-clamp recordings, Ca2+ imaging
Species:  Rat
Tissue:  Dopaminegic neurons
Response measured:  TRPM2-mediated whole-cell current and Ca2+ elevation
References:  6
Physiological Functions Click here for help
Oxidant stress sensor, mediator of H2O2 cell death (Note that these results are also reported in mouse)
Species:  Rat
Tissue:  Insuloma cells, microglia, neurons, pancreatic β-cells
References:  11,27,36,38,41
Cytokine/ROS (reactive oxygen species) production and inflammation (Note that these results are also reported in mouse and rat)
Species:  Human
Tissue:  Monocytes, macrophages, lymphocytes
References:  8,28,43,65,67
Insulin secretion (Note that these results are also reported in mouse and rat)
Species:  Human
Tissue:  Pancreatic β-cells
References:  2,38,55
Physiological Functions Comments
Activation of TRPM2 causes predisposition to apoptosis and cell death, inhibition of TRPM2 is neuroprotective [1,13,41,74].
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Trpm2tm1Yamo Trpm2tm1Yamo/Trpm2tm1Yamo
involves: 129S4/SvJae * C57BL/6J		 MGI:1351901  MP:0008750 abnormal interferon level PMID: 18542050 
Trpm2tm1Yamo Trpm2tm1Yamo/Trpm2tm1Yamo
involves: 129S4/SvJae * C57BL/6J		 MGI:1351901  MP:0008751 abnormal interleukin level PMID: 18542050 
Trpm2tm1Yamo Trpm2tm1Yamo/Trpm2tm1Yamo
involves: 129S4/SvJae * C57BL/6J		 MGI:1351901  MP:0002442 abnormal leukocyte physiology PMID: 18542050 
Trpm2tm1Yamo Trpm2tm1Yamo/Trpm2tm1Yamo
involves: 129S4/SvJae * C57BL/6J		 MGI:1351901  MP:0002451 abnormal macrophage physiology PMID: 18542050 
Trpm2tm1Yamo Trpm2tm1Yamo/Trpm2tm1Yamo
involves: 129S4/SvJae * C57BL/6J		 MGI:1351901  MP:0001876 decreased inflammatory response PMID: 18542050 
Trpm2tm1Yamo Trpm2tm1Yamo/Trpm2tm1Yamo
involves: 129S4/SvJae * C57BL/6J		 MGI:1351901  MP:0008719 impaired neutrophil recruitment PMID: 18542050 
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Amyotrophic lateral sclerosis-parkinsonism-dementia complex
OMIM: 105500
Orphanet: ORPHA90020
Role:  Loss of sustained ion influx through TRPM2 might contribute to the development of the disease state
References:  18-19
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human P1018L TRPM2, P1018L channels inactivate with in vitro results suggesting that the ability of TRPM2 to maintain sustained ion influx is a physiologically important function, disruption of which may contribute to disease states under certain conditions. 18
Disease:  Major affective disorder 1; MAFD1
Synonyms: Bipolar affective disorder
Manic depressive-psychosis
OMIM: 125480
Role:  Downregulation or mutation of TRPM2 may be associated with bipolar disorder.
References:  66,72
Disease:  Non-syndromic hereditary deafness
Synonyms: nonsyndromic deafness [Disease Ontology: DOID:0050563]
Disease Ontology: DOID:0050563
Role:  Downregulation or mutation of TRPM2 may be associated with nonsyndromic hereditary deafness.
References:  44
Gene Expression and Pathophysiology Click here for help
Overexpression.
Tissue or cell type:  All cell types.
Pathophysiology:  Cell death, apoptosis.
Species:  None
Technique: 
References:  1,5,34,36,41,49,52

References

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1. Aarts MM, Tymianski M. (2005) TRPMs and neuronal cell death. Pflugers Arch, 451 (1): 243-9. [PMID:16044308]

2. Bari MR, Akbar S, Eweida M, Kühn FJ, Gustafsson AJ, Lückhoff A, Islam MS. (2009) H2O2-induced Ca2+ influx and its inhibition by N-(p-amylcinnamoyl) anthranilic acid in the beta-cells: involvement of TRPM2 channels. J Cell Mol Med, 13 (9B): 3260-7. [PMID:19382906]

3. Beck A, Kolisek M, Bagley LA, Fleig A, Penner R. (2006) Nicotinic acid adenine dinucleotide phosphate and cyclic ADP-ribose regulate TRPM2 channels in T lymphocytes. FASEB J, 20 (7): 962-4. [PMID:16585058]

4. Belrose JC, Xie YF, Gierszewski LJ, MacDonald JF, Jackson MF. (2012) Loss of glutathione homeostasis associated with neuronal senescence facilitates TRPM2 channel activation in cultured hippocampal pyramidal neurons. Mol Brain, 5: 11. [PMID:22487454]

5. Chubanov V, Gudermann T, Schlingmann KP. (2005) Essential role for TRPM6 in epithelial magnesium transport and body magnesium homeostasis. Pflugers Arch, 451 (1): 228-34. [PMID:16075242]

6. Chung KK, Freestone PS, Lipski J. (2011) Expression and functional properties of TRPM2 channels in dopaminergic neurons of the substantia nigra of the rat. J Neurophysiol, 106 (6): 2865-75. [PMID:21900507]

7. Cruz-Torres I, Backos DS, Herson PS. (2020) Characterization and Optimization of the Novel Transient Receptor Potential Melastatin 2 Antagonist tatM2NX. Mol Pharmacol, 97 (2): 102-111. [PMID:31772034]

8. Di A, Gao XP, Qian F, Kawamura T, Han J, Hecquet C, Ye RD, Vogel SM, Malik AB. (2012) The redox-sensitive cation channel TRPM2 modulates phagocyte ROS production and inflammation. Nat Immunol, 13 (1): 29-34. [PMID:22101731]

9. Du J, Xie J, Yue L. (2009) Modulation of TRPM2 by acidic pH and the underlying mechanisms for pH sensitivity. J Gen Physiol, 134 (6): 471-88. [PMID:19917732]

10. Fonfria E, Marshall IC, Benham CD, Boyfield I, Brown JD, Hill K, Hughes JP, Skaper SD, McNulty S. (2004) TRPM2 channel opening in response to oxidative stress is dependent on activation of poly(ADP-ribose) polymerase. Br J Pharmacol, 143 (1): 186-92. [PMID:15302683]

11. Fonfria E, Marshall IC, Boyfield I, Skaper SD, Hughes JP, Owen DE, Zhang W, Miller BA, Benham CD, McNulty S. (2005) Amyloid beta-peptide(1-42) and hydrogen peroxide-induced toxicity are mediated by TRPM2 in rat primary striatal cultures. J Neurochem, 95 (3): 715-23. [PMID:16104849]

12. Fonfria E, Mattei C, Hill K, Brown JT, Randall A, Benham CD, Skaper SD, Campbell CA, Crook B, Murdock PR et al.. (2006) TRPM2 is elevated in the tMCAO stroke model, transcriptionally regulated, and functionally expressed in C13 microglia. J Recept Signal Transduct Res, 26 (3): 179-98. [PMID:16777714]

13. Gasser A, Glassmeier G, Fliegert R, Langhorst MF, Meinke S, Hein D, Krüger S, Weber K, Heiner I, Oppenheimer N et al.. (2006) Activation of T cell calcium influx by the second messenger ADP-ribose. J Biol Chem, 281 (5): 2489-96. [PMID:16316998]

14. Grubisha O, Rafty LA, Takanishi CL, Xu X, Tong L, Perraud AL, Scharenberg AM, Denu JM. (2006) Metabolite of SIR2 reaction modulates TRPM2 ion channel. J Biol Chem, 281 (20): 14057-65. [PMID:16565078]

15. Hara Y, Wakamori M, Ishii M, Maeno E, Nishida M, Yoshida T, Yamada H, Shimizu S, Mori E, Kudoh J et al.. (2002) LTRPC2 Ca2+-permeable channel activated by changes in redox status confers susceptibility to cell death. Mol Cell, 9 (1): 163-73. [PMID:11804595]

16. Haraguchi K, Kawamoto A, Isami K, Maeda S, Kusano A, Asakura K, Shirakawa H, Mori Y, Nakagawa T, Kaneko S. (2012) TRPM2 contributes to inflammatory and neuropathic pain through the aggravation of pronociceptive inflammatory responses in mice. J Neurosci, 32 (11): 3931-41. [PMID:22423113]

17. Heiner I, Eisfeld J, Halaszovich CR, Wehage E, Jüngling E, Zitt C, Lückhoff A. (2003) Expression profile of the transient receptor potential (TRP) family in neutrophil granulocytes: evidence for currents through long TRP channel 2 induced by ADP-ribose and NAD. Biochem J, 371 (Pt 3): 1045-53. [PMID:12564954]

18. Hermosura MC, Cui AM, Go RC, Davenport B, Shetler CM, Heizer JW, Schmitz C, Mocz G, Garruto RM, Perraud AL. (2008) Altered functional properties of a TRPM2 variant in Guamanian ALS and PD. Proc Natl Acad Sci USA, 105 (46): 18029-34. [PMID:19004782]

19. Hermosura MC, Garruto RM. (2007) TRPM7 and TRPM2-Candidate susceptibility genes for Western Pacific ALS and PD?. Biochim Biophys Acta, 1772 (8): 822-35. [PMID:17395433]

20. Herson PS, Dulock KA, Ashford ML. (1997) Characterization of a nicotinamide-adenine dinucleotide-dependent cation channel in the CRI-G1 rat insulinoma cell line. J Physiol (Lond.), 505 ( Pt 1): 65-76. [PMID:9409472]

21. Hill K, Benham CD, McNulty S, Randall AD. (2004) Flufenamic acid is a pH-dependent antagonist of TRPM2 channels. Neuropharmacology, 47 (3): 450-60. [PMID:15275834]

22. Hill K, McNulty S, Randall AD. (2004) Inhibition of TRPM2 channels by the antifungal agents clotrimazole and econazole. Naunyn Schmiedebergs Arch Pharmacol, 370 (4): 227-37. [PMID:15549272]

23. Hill K, Tigue NJ, Kelsell RE, Benham CD, McNulty S, Schaefer M, Randall AD. (2006) Characterisation of recombinant rat TRPM2 and a TRPM2-like conductance in cultured rat striatal neurones. Neuropharmacology, 50 (1): 89-97. [PMID:16260005]

24. Hiroi T, Wajima T, Negoro T, Ishii M, Nakano Y, Kiuchi Y, Mori Y, Shimizu S. (2013) Neutrophil TRPM2 channels are implicated in the exacerbation of myocardial ischaemia/reperfusion injury. Cardiovasc Res, 97 (2): 271-81. [PMID:23129587]

25. Hurne AM, Chai CL, Moerman K, Waring P. (2002) Influx of calcium through a redox-sensitive plasma membrane channel in thymocytes causes early necrotic cell death induced by the epipolythiodioxopiperazine toxins. J Biol Chem, 277 (35): 31631-8. [PMID:12063251]

26. Inada H, Iida T, Tominaga M. (2006) Different expression patterns of TRP genes in murine B and T lymphocytes. Biochem Biophys Res Commun, 350 (3): 762-7. [PMID:17027915]

27. Kaneko S, Kawakami S, Hara Y, Wakamori M, Itoh E, Minami T, Takada Y, Kume T, Katsuki H, Mori Y et al.. (2006) A critical role of TRPM2 in neuronal cell death by hydrogen peroxide. J Pharmacol Sci, 101 (1): 66-76. [PMID:16651700]

28. Kashio M, Sokabe T, Shintaku K, Uematsu T, Fukuta N, Kobayashi N, Mori Y, Tominaga M. (2012) Redox signal-mediated sensitization of transient receptor potential melastatin 2 (TRPM2) to temperature affects macrophage functions. Proc Natl Acad Sci USA, 109 (17): 6745-50. [PMID:22493272]

29. Katano M, Numata T, Aguan K, Hara Y, Kiyonaka S, Yamamoto S, Miki T, Sawamura S, Suzuki T, Yamakawa K et al.. (2012) The juvenile myoclonic epilepsy-related protein EFHC1 interacts with the redox-sensitive TRPM2 channel linked to cell death. Cell Calcium, 51 (2): 179-85. [PMID:22226147]

30. Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ et al.. (2011) Systematic and quantitative assessment of the ubiquitin-modified proteome. Mol Cell, 44 (2): 325-40. [PMID:21906983]

31. Kolisek M, Beck A, Fleig A, Penner R. (2005) Cyclic ADP-ribose and hydrogen peroxide synergize with ADP-ribose in the activation of TRPM2 channels. Mol Cell, 18 (1): 61-9. [PMID:15808509]

32. Kraft R, Grimm C, Frenzel H, Harteneck C. (2006) Inhibition of TRPM2 cation channels by N-(p-amylcinnamoyl)anthranilic acid. Br J Pharmacol, 148 (3): 264-73. [PMID:16604090]

33. Kraft R, Grimm C, Grosse K, Hoffmann A, Sauerbruch S, Kettenmann H, Schultz G, Harteneck C. (2004) Hydrogen peroxide and ADP-ribose induce TRPM2-mediated calcium influx and cation currents in microglia. Am J Physiol, Cell Physiol, 286 (1): C129-37. [PMID:14512294]

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