TRPM4 | Transient Receptor Potential channels | IUPHAR/BPS Guide to PHARMACOLOGY

TRPM4

Target id: 496

Nomenclature: TRPM4

Family: Transient Receptor Potential channels

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates.  » Email us

   GtoImmuPdb view: OFF :     TRPM4 has curated GtoImmuPdb data

Gene and Protein Information
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 6 1 1208 19q13.32 TRPM4 transient receptor potential cation channel subfamily M member 4 17,26-27,50
Mouse 6 1 1213 7 B4 Trpm4 transient receptor potential cation channel, subfamily M, member 4 26
Rat 6 1 1208 1q22 Trpm4 transient receptor potential cation channel, subfamily M, member 4 10
Previous and Unofficial Names
Long TRPC4 | Melastatin-like 2 | LTRPC4 | calcium-activated non-selective cation channel 1 | long transient receptor potential channel 4 | melastatin like 2 protein | TRPM4B | transient receptor potential cation channel
Database Links
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Orphanet
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Associated Proteins
Heteromeric Pore-forming Subunits
Name References
Not determined
Auxiliary Subunits
Name References
Not determined
Other Associated Proteins
Name References
calmodulin 29
ATP-binding cassette, sub-family C (CFTR/MRP), member 8 5,41,49
Associated Protein Comments
Results from Sala-Rabanal et al (2012) contradict the postulation that SUR1 modulates TRPM4, by finding no evidence of functional or structural association between TRPM4 and SUR1 [36].
Functional Characteristics
γ = 23 pS (within the range 60 to +60 mV); permeable to monovalent cations; impermeable to Ca2+; strong outward rectification; slow activation at positive potentials, rapid deactivation at negative potentials, deactivation blocked by decavanadate
Ion Selectivity and Conductance
Species:  Human
Rank order:  Na+ > K+ > Cs+ > Li+ [25.0 pS]
References:  17,26-27
Ion Selectivity and Conductance Comments
Ca2+ impermeable.
Voltage Dependence
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -20.0 – 60.0 33.9 26,29,32,45 HEK 293 cells. Human
Inactivation  - 40.6 45
Voltage Dependence Comments
Range of voltage activation depends on intracellular Ca2+ concentration, PIP2, PKC phosphorylation, presence of calmodulin [24,26,29,31-32].
Other channel blockers
Intracellular nucleotides including ATP, ADP, adenosine 5'-monophosphate and AMP-PNP with an IC50 range of 1.3-1.9 μM
Physical activators (Human)
Membrane depolarization (V½ = -20 mV to + 60 mV dependent upon conditions) in the presence of elevated [Ca2+]i, heat (Q10 = 8.5 @ +25 mV between 15 and 25°C)

Download all structure-activity data for this target as a CSV file

Activators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Concentration range (M) Holding voltage (mV) Reference
BTP2 Hs Agonist 8.1 pEC50 - -80.0 43
pEC50 8.1 (EC50 8x10-9 M) [43]
Holding voltage: -80.0 mV
decavanadate Hs Agonist 5.7 pEC50 - -100.0 28
pEC50 5.7 (EC50 1.9x10-9 M) [28]
Holding voltage: -100.0 mV
PIP2 Hs Agonist 5.3 pEC50 - 100.0 24
pEC50 5.3 [24]
Holding voltage: 100.0 mV
PIP2 Mm Agonist 5.2 pEC50 - -80.0 52
pEC50 5.2 [52]
Holding voltage: -80.0 mV
intracellular Ca2+ Hs Agonist 3.9 – 6.3 pEC50 - -100.0 – 100.0 24,28-29,43
pEC50 3.9 – 6.3 (EC50 1.4x10-4 – 5x10-7 M) [24,28-29,43]
Holding voltage: -100.0 – 100.0 mV
View species-specific activator tables
Activator Comments
Ca2+ affinity is regulated by PIP2, phosphorylation by PKC. Decreased Ca2+ affinity during desensitisation, strong desensitisation in inside-out patches [24,26,29,31-32]. U73122 prevents TRPM4 desensitisation and rescues activity [24]. Potentiation by BTP2 is increased at positive holding potentials [43].
Gating inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Concentration range (M) Holding voltage (mV) Reference
clotrimazole Hs Antagonist - - 1x10-6 - 1x10-5 100.0 33
Conc range: 1x10-6 - 1x10-5 M [33]
Holding voltage: 100.0 mV
compound 6 [PMID: 29579323] Hs - 6.4 pIC50 - - 34
pIC50 6.4 (IC50 4x10-7 M) [34]
Description: In a fluorescence cell‐based screening assay that monitors Na+ influx using the intracellular Na+ specific dye Asante natrium green‐II.
compound 5 [PMID: 29579323] Hs - 5.8 pIC50 - - 34
pIC50 5.8 (IC50 1.5x10-6 M) [34]
Description: In a fluorescence cell‐based screening assay that monitors Na+ influx using the intracellular Na+ specific dye Asante natrium green‐II.
ADP Hs Antagonist 5.7 pIC50 - 100.0 30
pIC50 5.7 [30]
Holding voltage: 100.0 mV
flufenamic acid Mm Antagonist 5.6 pIC50 - 100.0 45
pIC50 5.6 (IC50 2.8x10-6 M) [45]
Holding voltage: 100.0 mV
ATP Hs Antagonist 4.9 pIC50 - 100.0 30
pIC50 4.9 [30]
Holding voltage: 100.0 mV
adenosine 5'-monophosphate Hs Antagonist 4.7 pIC50 - 100.0 30
pIC50 4.7 [30]
Holding voltage: 100.0 mV
AMP-PNP Hs Antagonist 4.7 pIC50 - 100.0 30
pIC50 4.7 [30]
Holding voltage: 100.0 mV
View species-specific gating inhibitor tables
Gating Inhibitor Comments
We have included the TRPM4 inhibitors compound 5 and compound 6 (both from Ozhathil et al., 2018 [34]) as gating inhibitors as they are anthranilic amide derivatives of the gating inhibitor flufenamic acid.
Channel Blockers
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Concentration range (M) Holding voltage (mV) Reference
ATP Mm Antagonist 6.1 pIC50 - 100.0 45
pIC50 6.1 [45]
Holding voltage: 100.0 mV
ATP Hs Antagonist 5.8 pIC50 - 100.0 30
pIC50 5.8 [30]
Holding voltage: 100.0 mV
9-phenanthrol Hs - 4.6 – 4.8 pIC50 - - 11
pIC50 4.6 – 4.8 (IC50 2.28x10-5 – 1.67x10-5 M) [11]
spermine Mm Antagonist 4.5 pIC50 - 100.0 45
pIC50 4.5 [45]
Holding voltage: 100.0 mV
spermine Hs Antagonist 4.2 pIC50 - 100.0 30
pIC50 4.2 (IC50 6.1x10-5 M) [30]
Holding voltage: 100.0 mV
adenosine Hs - 3.2 pIC50 - -
pIC50 3.2 (IC50 6.3x10-4 M)
View species-specific channel blocker tables
Channel Blocker Comments
Pore mutation Asp984 -> Ala results in a non-functional channel with a dominant negative phenotype; block by spermine is reduced by pore mutation Glu981 -> Ala [27].
Immunopharmacology Comments
TRPM4 is expressed on human T cells, mouse dendritic cells, human and mouse monocytes/macrophages, and mouse mast cells [35]. It is activated by antigen receptor-mediated Ca2+ mobilization (influx) [17]. Inhibition of TRPM4 function (genetic or pharmacological) in mouse experimental autoimmune encephalomyelitis (EAE) reduced clinical symptoms and slowed disease progression [3], indicating the neuroprotective potential of TRPM4 inhibitors.
Cell Type Associations
Immuno Cell Type:  Mast cells
Cell Ontology Term:   mast cell (CL:0000097)
Comment:  TRPM4 is involved in mast cell function.
References:  46-47
Immuno Cell Type:  T cells
Comment:  TRPM4 is involved in T cell cytokine production and motility.
References:  46
Immuno Cell Type:  Dendritic cells
Cell Ontology Term:   dendritic cell (CL:0000451)
Comment:  TRPM4 is essential for the migration of DCs.
References:  1,46
Immuno Cell Type:  Macrophages & monocytes
Comment:  TRPM4 is involved in macrophage cytokine production and phagocytosis.
References:  39,46
Immuno Process Associations
Immuno Process:  Inflammation
GO Annotations:  Associated to 2 GO processes
GO:0002407 dendritic cell chemotaxis ISS
GO:0002724 regulation of T cell cytokine production IDA
Immuno Process:  T cell (activation)
GO Annotations:  Associated to 2 GO processes
GO:0002724 regulation of T cell cytokine production IDA
click arrow to show/hide IEA associations
GO:0002250 adaptive immune response IEA
Immuno Process:  B cell (activation)
GO Annotations:  Associated to 2 GO processes
GO:0002724 regulation of T cell cytokine production IDA
click arrow to show/hide IEA associations
GO:0002250 adaptive immune response IEA
Immuno Process:  Immune regulation
GO Annotations:  Associated to 1 GO processes
GO:0002724 regulation of T cell cytokine production IDA
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 1 GO processes
GO:0002724 regulation of T cell cytokine production IDA
Immuno Process:  Chemotaxis & migration
GO Annotations:  Associated to 1 GO processes
GO:0002407 dendritic cell chemotaxis ISS
Tissue Distribution
Small intestine, prostate, colon, kidneys (proximal convoluted tubule, distal convoluted tubule, proximal straight tubule, loop of Henle, cortical collecting duct), testes, heart, lymphocytes, spleen, lung, brain, pituitary, skeletal muscle, stomach, adipose tissue, bone.
Species:  Human
Technique:  Northern blot, Western blot, RT-PCR, TaqMan qPCR
References:  4,8,17-18,26,50
Thymocytes, intestine, aortic endothelium, placenta, pancreas, lung, bladder.
Species:  Mouse
Technique:  Northern blot, Western blot
References:  16-17,26,51
Cerebral arteries, smooth muscle cells, magnocellular cells in supraoptic and paraventricular nuclei (hypothalamus).
Species:  Rat
Technique:  RT-PCR
References:  7,44
Functional Assays
Patch clamp (whole-cell and single-channel recordings).
Species:  Human
Tissue:  Overexpression in HEK 293 cells.
Response measured:  Current activation, negative feedback on Ca2+ entry, depolarisation of cell membrane potential.
References:  18,24,26-29,43
Patch clamp (whole-cell and single-channel recordings).
Species:  Human
Tissue:  Jurkat cells.
Response measured:  PHA-induced interleukin-2 release, oscillation of intracellular Ca2+ concentration, cell membrane potential.
References:  17
Whole-cell patch clamp, Ca2+ analysis, down-regulation of TRPM4 by expression of short splice variant TRPM4a.
Species:  Rat
Tissue:  β-cell model insulinoma INS-1 cells.
Response measured:  Glucose-induced insulin secretion, voltage clamp analysis.
References:  6
Whole-cell patch clamp, arteriography.
Species:  Rat
Tissue:  Smooth muscle cells, cerebral arteries.
Response measured:  Single-channel current, membrane potential, vessel diameter and tension.
References:  7
Patch clamp (whole-cell and single-channel recordings).
Species:  Mouse
Tissue:  Overexpression in HEK 293 cells.
Response measured:  Current activation, negative feedback on Ca2+ entry, depolarisation of cell membrane potential.
References:  26,45
Patch clamp (whole-cell and single-channel recordings).
Species:  Mouse
Tissue:  Cerebral artery smooth muscle cells.
Response measured:  Protein kinase C delta activity is required for membrane localization and activity.
References:  9
Physiological Functions
Candidate for endogenous calcium-activated cation (CAN) channels, negative feedback regulator of Ca2+ entry, involved in oscillatory electrical activity and the generation of the Bayliss effect in smooth muscle.
Species:  Human
Tissue:  Widely expressed.
References:  14,18,26,32
Putative role in controlling glucagon secretion from pancreatic α-cells and perhaps glucose homeostasis.
Species:  Mouse
Tissue:  Pancreas
References:  20,23
Limits catecholamine release from chromaffin cells, thereby contributing to increased sympathetic tone and hypertension.
Species:  Mouse
Tissue:  Adrenal medulla
References:  21
Critical for the proper functioning of monocytes/macrophages and the efficiency of the subsequent response to infection; also important for mast cell migration.
Species:  Mouse
Tissue:  Peripheral blood and bone marrow
References:  39-40,48
Mediates axonal and neuronal degeneration in experimental autoimmune encephalomyelitis and multiple sclerosis.
Species:  Mouse
Tissue:  Brain
References:  37
Role in lipopolysaccharide (LPS)-induced reactive oxygen species (ROS)-mediated endothelial cell death.
Species:  Mouse
Tissue:  Endothelium
References:  2
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Trpm4tm1.1Mfre Trpm4tm1.1Mfre/Trpm4tm1.1Mfre
involves: 129S1/Sv * 129X1/SvJ * BALB/cJ
MGI:1915917  MP:0004231 abnormal calcium ion homeostasis PMID: 17293867 
Trpm4tm1.1Knt Trpm4tm1.1Knt/Trpm4tm1.1Knt
Not Specified
MGI:1915917  MP:0002376 abnormal dendritic cell physiology PMID: 18758465 
Trpm4tm1.1Knt|Trpm5tm1Csz Trpm4tm1.1Knt/Trpm4tm1.1Knt,Trpm5tm1Csz/Trpm5tm1Csz
involves: 129S1/Sv * 129X1/SvJ
MGI:1861718  MGI:1915917  MP:0002376 abnormal dendritic cell physiology PMID: 18758465 
Trpm4tm1.1Knt Trpm4tm1.1Knt/Trpm4tm1.1Knt
Not Specified
MGI:1915917  MP:0008127 decreased dendritic cell number PMID: 18758465 
Trpm4tm1.1Knt|Trpm5tm1Csz Trpm4tm1.1Knt/Trpm4tm1.1Knt,Trpm5tm1Csz/Trpm5tm1Csz
involves: 129S1/Sv * 129X1/SvJ
MGI:1861718  MGI:1915917  MP:0008127 decreased dendritic cell number PMID: 18758465 
Trpm4tm1.1Mfre Trpm4tm1.1Mfre/Trpm4tm1.1Mfre
involves: 129S1/Sv * 129X1/SvJ * BALB/cJ
MGI:1915917  MP:0005596 increased susceptibility to type I hypersensitivity reaction PMID: 17293867 
Trpm4tm1.1Mfre Trpm4tm1.1Mfre/Trpm4tm1.1Mfre
involves: 129S1/Sv * 129X1/SvJ * BALB/cJ
MGI:1915917  MP:0003070 increased vascular permeability PMID: 17293867 
Clinically-Relevant Mutations and Pathophysiology
Disease:  Brugada syndrome
Disease Ontology: DOID:0050451
Orphanet: ORPHA130
References:  19
Disease:  Progressive familial heart block, type IB, PFHB1B
Synonyms: Familial progressive cardiac conduction defect [Orphanet: ORPHA871]
OMIM: 604559
Orphanet: ORPHA871
Clinically-Relevant Mutations and Pathophysiology Comments
TRPM4 has been implicated to play a role in hyper-responsiveness in immune cells, induction of pro-inflammatory conditions, allergy, defective surfactant secretion in pneumocytes, defective Bayliss effect, trigger for paroxysmal depolarisation shift, spreading depression-like hypoxic depolarisation, stroke, and cardiac conductance disturbances including cardiac hypertrophy and arrythmia; atrioventricular block or right bundle branch block [12-13,17,25,38,41-42].
Gene Expression and Pathophysiology
Overexpression.
Tissue or cell type:  Skeletal and cardiac muscle.
Pathophysiology:  Muscular dystrophy and cardiomyopathy.
Species:  None
Technique: 
References:  15
General Comments
Human: long splice-variant TRPM4b (1214 AA), short splice-variant TRPM4a (1040 AA, lacks first 174 AA), shortest splice variant TRPM4c (537 AA, lacks N-terminal) [26].

Mouse: two short splice variants from brain [22].

References

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1. Barbet G, Demion M, Moura IC, Serafini N, Léger T, Vrtovsnik F, Monteiro RC, Guinamard R, Kinet JP, Launay P. (2008) The calcium-activated nonselective cation channel TRPM4 is essential for the migration but not the maturation of dendritic cells. Nat. Immunol., 9 (10): 1148-56. [PMID:18758465]

2. Becerra A, Echeverría C, Varela D, Sarmiento D, Armisén R, Nuñez-Villena F, Montecinos M, Simon F. (2011) Transient receptor potential melastatin 4 inhibition prevents lipopolysaccharide-induced endothelial cell death. Cardiovasc. Res., 91 (4): 677-84. [PMID:21565835]

3. Bianchi B, Smith PA, Abriel H. (2018) The ion channel TRPM4 in murine experimental autoimmune encephalomyelitis and in a model of glutamate-induced neuronal degeneration. Mol Brain, 11 (1): 41. [PMID:29996905]

4. Chabardes-Garonne D, Mejean A, Aude JC, Cheval L, Di Stefano A, Gaillard MC, Imbert-Teboul M, Wittner M, Balian C, Anthouard V, Robert C, Segurens B, Wincker P, Weissenbach J, Doucet A, Elalouf JM. (2003) A panoramic view of gene expression in the human kidney. Proc. Natl. Acad. Sci. U.S.A., 100 (23): 13710-5. [PMID:14595018]

5. Chen M, Dong Y, Simard JM. (2003) Functional coupling between sulfonylurea receptor type 1 and a nonselective cation channel in reactive astrocytes from adult rat brain. J. Neurosci., 23 (24): 8568-77. [PMID:13679426]

6. Cheng H, Beck A, Launay P, Gross SA, Stokes AJ, Kinet JP, Fleig A, Penner R. (2007) TRPM4 controls insulin secretion in pancreatic beta-cells. Cell Calcium, 41 (1): 51-61. [PMID:16806463]

7. Earley S, Waldron BJ, Brayden JE. (2004) Critical role for transient receptor potential channel TRPM4 in myogenic constriction of cerebral arteries. Circ. Res., 95 (9): 922-9. [PMID:15472118]

8. Fonfria E, Murdock PR, Cusdin FS, Benham CD, Kelsell RE, McNulty S. (2006) Tissue distribution profiles of the human TRPM cation channel family. J. Recept. Signal Transduct. Res., 26 (3): 159-78. [PMID:16777713]

9. Garcia ZI, Bruhl A, Gonzales AL, Earley S. (2011) Basal protein kinase Cδ activity is required for membrane localization and activity of TRPM4 channels in cerebral artery smooth muscle cells. Channels (Austin), 5 (3): 210-4. [PMID:21406958]

10. Gibbs RA, Weinstock GM, Metzker ML, Muzny DM, Sodergren EJ, Scherer S, Scott G, Steffen D, Worley KC, Burch PE, Okwuonu G, Hines S, Lewis L, DeRamo C, Delgado O, Dugan-Rocha S, Miner G, Morgan M, Hawes A, Gill R, Celera RA, Adams MD, Amanatides PG, Baden-Tillson H, Barnstead M, Chin S, Evans CA, Ferriera S, Fosler C, Glodek A, Gu Z, Jennings D, Kraft CL, Nguyen T, Pfannkoch CM, Sitter C, Sutton GG, Venter JC, Woodage T, Smith D, Lee HM, Gustafson E, Cahill P, Kana A, Doucette-Stamm L, Weinstock K, Fechtel K, Weiss RB, Dunn DM, Green ED, Blakesley RW, Bouffard GG, De Jong PJ, Osoegawa K, Zhu B, Marra M, Schein J, Bosdet I, Fjell C, Jones S, Krzywinski M, Mathewson C, Siddiqui A, Wye N, McPherson J, Zhao S, Fraser CM, Shetty J, Shatsman S, Geer K, Chen Y, Abramzon S, Nierman WC, Havlak PH, Chen R, Durbin KJ, Egan A, Ren Y, Song XZ, Li B, Liu Y, Qin X, Cawley S, Worley KC, Cooney AJ, D'Souza LM, Martin K, Wu JQ, Gonzalez-Garay ML, Jackson AR, Kalafus KJ, McLeod MP, Milosavljevic A, Virk D, Volkov A, Wheeler DA, Zhang Z, Bailey JA, Eichler EE, Tuzun E, Birney E, Mongin E, Ureta-Vidal A, Woodwark C, Zdobnov E, Bork P, Suyama M, Torrents D, Alexandersson M, Trask BJ, Young JM, Huang H, Wang H, Xing H, Daniels S, Gietzen D, Schmidt J, Stevens K, Vitt U, Wingrove J, Camara F, Mar Albà M, Abril JF, Guigo R, Smit A, Dubchak I, Rubin EM, Couronne O, Poliakov A, Hübner N, Ganten D, Goesele C, Hummel O, Kreitler T, Lee YA, Monti J, Schulz H, Zimdahl H, Himmelbauer H, Lehrach H, Jacob HJ, Bromberg S, Gullings-Handley J, Jensen-Seaman MI, Kwitek AE, Lazar J, Pasko D, Tonellato PJ, Twigger S, Ponting CP, Duarte JM, Rice S, Goodstadt L, Beatson SA, Emes RD, Winter EE, Webber C, Brandt P, Nyakatura G, Adetobi M, Chiaromonte F, Elnitski L, Eswara P, Hardison RC, Hou M, Kolbe D, Makova K, Miller W, Nekrutenko A, Riemer C, Schwartz S, Taylor J, Yang S, Zhang Y, Lindpaintner K, Andrews TD, Caccamo M, Clamp M, Clarke L, Curwen V, Durbin R, Eyras E, Searle SM, Cooper GM, Batzoglou S, Brudno M, Sidow A, Stone EA, Venter JC, Payseur BA, Bourque G, López-Otín C, Puente XS, Chakrabarti K, Chatterji S, Dewey C, Pachter L, Bray N, Yap VB, Caspi A, Tesler G, Pevzner PA, Haussler D, Roskin KM, Baertsch R, Clawson H, Furey TS, Hinrichs AS, Karolchik D, Kent WJ, Rosenbloom KR, Trumbower H, Weirauch M, Cooper DN, Stenson PD, Ma B, Brent M, Arumugam M, Shteynberg D, Copley RR, Taylor MS, Riethman H, Mudunuri U, Peterson J, Guyer M, Felsenfeld A, Old S, Mockrin S, Collins F. (2004) Genome sequence of the Brown Norway rat yields insights into mammalian evolution. Nature, 428 (6982): 493-521. [PMID:15057822]

11. Grand T, Demion M, Norez C, Mettey Y, Launay P, Becq F, Bois P, Guinamard R. (2008) 9-phenanthrol inhibits human TRPM4 but not TRPM5 cationic channels. Br. J. Pharmacol., 153 (8): 1697-705. [PMID:18297105]

12. Guinamard R, Chatelier A, Demion M, Potreau D, Patri S, Rahmati M, Bois P. (2004) Functional characterization of a Ca(2+)-activated non-selective cation channel in human atrial cardiomyocytes. J. Physiol. (Lond.), 558 (Pt 1): 75-83. [PMID:15121803]

13. Guinamard R, Chatelier A, Lenfant J, Bois P. (2004) Activation of the Ca(2+)-activated nonselective cation channel by diacylglycerol analogues in rat cardiomyocytes. J. Cardiovasc. Electrophysiol., 15 (3): 342-8. [PMID:15030426]

14. Hofmann T, Chubanov V, Gudermann T, Montell C. (2003) TRPM5 is a voltage-modulated and Ca(2+)-activated monovalent selective cation channel. Curr. Biol., 13 (13): 1153-8. [PMID:12842017]

15. Iwata Y, Katanosaka Y, Arai Y, Komamura K, Miyatake K, Shigekawa M. (2003) A novel mechanism of myocyte degeneration involving the Ca2+-permeable growth factor-regulated channel. J. Cell Biol., 161 (5): 957-67. [PMID:12796481]

16. Jang Y, Lee Y, Kim SM, Yang YD, Jung J, Oh U. (2012) Quantitative analysis of TRP channel genes in mouse organs. Arch. Pharm. Res., 35 (10): 1823-30. [PMID:23139135]

17. Launay P, Cheng H, Srivatsan S, Penner R, Fleig A, Kinet JP. (2004) TRPM4 regulates calcium oscillations after T cell activation. Science, 306 (5700): 1374-7. [PMID:15550671]

18. Launay P, Fleig A, Perraud AL, Scharenberg AM, Penner R, Kinet JP. (2002) TRPM4 is a Ca2+-activated nonselective cation channel mediating cell membrane depolarization. Cell, 109 (3): 397-407. [PMID:12015988]

19. Liu H, Chatel S, Simard C, Syam N, Salle L, Probst V, Morel J, Millat G, Lopez M, Abriel H et al.. (2013) Molecular genetics and functional anomalies in a series of 248 Brugada cases with 11 mutations in the TRPM4 channel. PLoS ONE, 8 (1): e54131. [PMID:23382873]

20. Marigo V, Courville K, Hsu WH, Feng JM, Cheng H. (2009) TRPM4 impacts on Ca2+ signals during agonist-induced insulin secretion in pancreatic beta-cells. Mol. Cell. Endocrinol., 299 (2): 194-203. [PMID:19063936]

21. Mathar I, Vennekens R, Meissner M, Kees F, Van der Mieren G, Camacho Londoño JE, Uhl S, Voets T, Hummel B, van den Bergh A et al.. (2010) Increased catecholamine secretion contributes to hypertension in TRPM4-deficient mice. J. Clin. Invest., 120 (9): 3267-79. [PMID:20679729]

22. Murakami M, Xu F, Miyoshi I, Sato E, Ono K, Iijima T. (2003) Identification and characterization of the murine TRPM4 channel. Biochem. Biophys. Res. Commun., 307 (3): 522-8. [PMID:12893253]

23. Nelson PL, Zolochevska O, Figueiredo ML, Soliman A, Hsu WH, Feng JM, Zhang H, Cheng H. (2011) Regulation of Ca(2+)-entry in pancreatic α-cell line by transient receptor potential melastatin 4 plays a vital role in glucagon release. Mol. Cell. Endocrinol., 335 (2): 126-34. [PMID:21238535]

24. Nilius B, Mahieu F, Prenen J, Janssens A, Owsianik G, Vennekens R, Voets T. (2006) The Ca2+-activated cation channel TRPM4 is regulated by phosphatidylinositol 4,5-biphosphate. EMBO J., 25 (3): 467-78. [PMID:16424899]

25. Nilius B, Owsianik G, Voets T, Peters JA. (2007) Transient receptor potential cation channels in disease. Physiol. Rev., 87 (1): 165-217. [PMID:17237345]

26. Nilius B, Prenen J, Droogmans G, Voets T, Vennekens R, Freichel M, Wissenbach U, Flockerzi V. (2003) Voltage dependence of the Ca2+-activated cation channel TRPM4. J. Biol. Chem., 278 (33): 30813-20. [PMID:12799367]

27. Nilius B, Prenen J, Janssens A, Owsianik G, Wang C, Zhu MX, Voets T. (2005) The selectivity filter of the cation channel TRPM4. J. Biol. Chem., 280 (24): 22899-906. [PMID:15845551]

28. Nilius B, Prenen J, Janssens A, Voets T, Droogmans G. (2004) Decavanadate modulates gating of TRPM4 cation channels. J. Physiol. (Lond.), 560 (Pt 3): 753-65. [PMID:15331675]

29. Nilius B, Prenen J, Tang J, Wang C, Owsianik G, Janssens A, Voets T, Zhu MX. (2005) Regulation of the Ca2+ sensitivity of the nonselective cation channel TRPM4. J. Biol. Chem., 280 (8): 6423-33. [PMID:15590641]

30. Nilius B, Prenen J, Voets T, Droogmans G. (2004) Intracellular nucleotides and polyamines inhibit the Ca2+-activated cation channel TRPM4b. Pflugers Arch., 448 (1): 70-5. [PMID:14758478]

31. Nilius B, Talavera K, Owsianik G, Prenen J, Droogmans G, Voets T. (2005) Gating of TRP channels: a voltage connection?. J. Physiol. (Lond.), 567 (Pt 1): 35-44. [PMID:15878939]

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Kristopher T Kahle, David E. Clapham.
Transient Receptor Potential channels: TRPM4. Last modified on 13/09/2018. Accessed on 19/11/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=496.