Nomenclature: TRPM5

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. 

Contents

Gene and Protein Information
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 6 1 1165 11p15.5 TRPM5 transient receptor potential cation channel, subfamily M, member 5 23
Mouse 6 1 1158 7 F5 Trpm5 transient receptor potential cation channel, subfamily M, member 5 5
Rat 6 1 1158 1q42 Trpm5 transient receptor potential cation channel, subfamily M, member 5
Previous and Unofficial Names
MTR1
TRP-T
L-TRPC5
LOC365391
Trpm5_predicted
transient receptor potential cation channel subfamily M member 5
transient receptor potential cation channel, subfamily M, member 5
transient receptor potential cation channel, subfamily M, member 5 (predicted)
9430099A16Rik
Database Links
Ensembl Gene
Entrez Gene
GeneCards
GenitoUrinary Development Molecular Anatomy Project
HomoloGene
Human Protein Reference Database
InterPro
KEGG Gene
OMIM
PharmGKB Gene
PhosphoSitePlus
Protein Ontology (PRO)
RefSeq Nucleotide
RefSeq Protein
TreeFam
UniGene Hs.
UniProtKB
Wikipedia
Functional Characteristics
γ = 15-25 pS; conducts monovalent cations selectively (PCa/PNa = 0.05); strong outward rectification; slow activation at positive potentials, rapid inactivation at negative potentials; activated and subsequently desensitized by [Ca2+]I
Ion Selectivity and Conductance Comments
Nonselective for monovalent cations, impermeable to divalent cations. Average single-channel conductance of mTRPM5 is 20-25 pS [8,24]. Instantaneous single-channel conductance is linear [24].
Voltage Dependence
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  100.0 18.8 28 HEK 293 cells. Mouse
Inactivation  - -
Deactivation  - 9.1 – 50.2 8,28
Comments  Heat activation of TRPM5 is the result of a drastic leftward shift of the voltage dependence of activation (-7.0 mV.°C-1) [25].
Physical activators (Human)
membrane depolarization (V½ = 0 to + 120 mV dependent upon conditions), heat (Q10 = 10.3 @ -75 mV between 15 and 25°C)
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
intracellular Ca2+ Hs - 6.1 – 6.2 pEC50 - -
pEC50 6.1 – 6.2 (EC50 6.35x10-7 – 8.4x10-7 M) transient activation
intracellular Ca2+ Mm Agonist 4.2 – 6.2 (median: 4.7) pEC50 - -80.0 – 80.0 8,14,28
pEC50 4.2 – 6.2 (median: 4.7) [8,14,28]
Holding voltage: -80.0 – 80.0 mV
rosiglitazone Hs - - - - - 17
[17]
View species-specific activator tables
Activator Comments
Desensitisation of TRPM5 is modulated by PIP2, which acts as a co-factor for activation [14]. Human TRPM5 expressed in HEK293 cells is sensitive to rapid but not slow elevations in Ca2+ [24]. Arachidonic acid (10µM) activates mouse Trpm5 in transfected HEK293 cells [21]. Flash photolysis of caged IP3 activates mTrpm5 current in whole-cell but not excised patches [30].

In a calcium uncaging experiment mouse Trpm5 is activated with a time constant (τ) of 1.9ms at 100mV [28].
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
flufenamic acid Hs - 4.62 pIC50 - -
pIC50 4.62 (IC50 2.4x10-5 M)
intracellular spermine Hs - 4.43 pIC50 - -
pIC50 4.43 (IC50 3.7x10-5 M)
Extracellular H+ Hs - 3.2 pIC50 - -
pIC50 3.2 (IC50 6.3x10-4 M)
Channel Blocker Comments
TRPM5 is sensitive to pH below 7.0, with complete block at around pH 5.9 [15]. Histidines in the pore region (His-934) and a glutamate in the S3-S4 extracellular linker (Glu-830) enhance sensitivity to proton block [15].
Tissue Distribution
Intestines, pancreas, prostate, kidney, pituitary
Species:  Human
Technique:  RT-PCR
References:  1,6,18
Taste tissue, olfactory epithelium, pancreatic β-cells, stomach, intestines, uterus, testes, cerebellar Purkinje cells, vasopressin-secreting hypothalamic neurons.
Species:  Mouse
Technique:  Immunocytochemistry, northern blot, in situ hybridisation.
References:  3,7,10-12,22,29
Vasopressin-secreting hypothalamic neurons
Species:  Rat
Technique:  Immunocytochemistry, RT-PCR
References:  26
Functional Assays
Patch clamp (whole-cell and single-channel recordings).
Species:  Mouse
Tissue:  HEK 293 or CHO cells transfected with TRPM5 vector.
Response measured:  Ca2+ evoked currents.
References:  8,14,19-20,22,24-25,28-29
Two-electrode voltage clamp technique.
Species:  Mouse
Tissue:  Xenopus laevis oocytes injected with TRPM5 cDNA.
Response measured:  Ca2+ evoked currents.
References:  22
Ca2+ imaging
Species:  Mouse
Tissue:  Taste cells
Response measured:  Ca2+ elevation in response to chemical activators or membrane depolarization
References:  9
Patch clamp (whole-cell recordings), Ca2+ uncaging, Ca2+ imaging, glucose-induced insulin secretion
Species:  Mouse
Tissue:  Pancreatic islet cells
Response measured:  Ca2+ evoked currents, glucose-stimulated Ca2+ oscillations and insulin secretion
References:  3
Field-potential recording, Ca2+ imaging
Species:  Mouse
Tissue:  Olfactory epithelium
Response measured:  Odorant-induced field potentials, odorant-induced Ca2+ elevations
References:  13
Patch clamp (whole-cell recordings), Ca2+ imaging
Species:  Mouse
Tissue:  Taste cells
Response measured:  Linoleic-acid evoked currents and Ca2+ elevations
References:  16
Patch clamp (whole-cell recordings), Ca2+ imaging
Species:  Mouse
Tissue:  Cerebellar slice
Response measured:  Depolarization-induced slow current and Ca2+ elevations
References:  10
Patch clamp (whole-cell recordings)
Species:  Human
Tissue:  HEK293 cells expressing TRPM5
Response measured:  Ca2+ and temperature evoked currents
References:  25
Patch clamp (whole-cell and single-channel recordings)
Species:  Human
Tissue:  Transfected HEK293 cells (human), taste cells from knockout mice
Response measured:  Ca2+ and IP3 evoked currents
References:  25
Patch clamp (whole-cell recordings), Ca2+ imaging
Species:  Human
Tissue:  Human colon adenocarcinoma goblet cells (HT29-18N2, serum starved)
Response measured:  Ca2+-induced currents and Ca2+ elevations
References:  18
Physiological Functions
Bitter, sweet, umami receptor channel. Free fatty acid receptor channel.
Species:  Mouse
Tissue:  Taste tissue.
References:  4,16,22,25,29
Insulin secretion
Species:  Mouse
Tissue:  Pancreatic islets
References:  2-3
Irritant odor receptor channel
Species:  Mouse
Tissue:  Olfactory epithelium
References:  12-13,27
Mucin 5AC (MUC5AC) secretion
Species:  Human
Tissue:  Colonic goblet cells
References:  18
Phenotypes, Alleles and Disease Models Mouse data from MGI

Show »

Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Trpm5tm1Csz Trpm5tm1Csz/Trpm5tm1Csz
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
MGI:1861718  MP:0004210 abnormal bitter taste sensitivity PMID: 12581520 
Trpm5tm1Sdmk Trpm5tm1Sdmk/Trpm5tm1Sdmk
involves: C57BL/6
MGI:1861718  MP:0004210 abnormal bitter taste sensitivity PMID: 16355226 
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 
Trpm5tm1Csz Trpm5tm1Csz/Trpm5tm1Csz
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
MGI:1861718  MP:0001985 abnormal gustatory system physiology PMID: 12581520 
Trpm5tm1Sdmk Trpm5tm1Sdmk/Trpm5tm1Sdmk
involves: C57BL/6
MGI:1861718  MP:0004212 abnormal salty taste sensitivity PMID: 16355226 
Trpm5tm1Sdmk Trpm5tm1Sdmk/Trpm5tm1Sdmk
involves: C57BL/6
MGI:1861718  MP:0004211 abnormal sour taste sensitivity PMID: 16355226 
Trpm5tm1Csz Trpm5tm1Csz/Trpm5tm1Csz
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
MGI:1861718  MP:0004209 abnormal sweet taste sensitivity PMID: 12581520 
Trpm5tm1Sdmk Trpm5tm1Sdmk/Trpm5tm1Sdmk
involves: C57BL/6
MGI:1861718  MP:0004209 abnormal sweet taste sensitivity PMID: 16355226 
Trpm5tm1Csz Trpm5tm1Csz/Trpm5tm1Csz
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
MGI:1861718  MP:0001986 abnormal taste sensitivity PMID: 12581520 
Trpm5tm1Sdmk Trpm5tm1Sdmk/Trpm5tm1Sdmk
involves: C57BL/6
MGI:1861718  MP:0001986 abnormal taste sensitivity PMID: 16355226 
Trpm5tm1Dgen Trpm5tm1Dgen/Trpm5tm1Dgen
B6.129P2-Trpm5
MGI:1861718  MP:0001986 abnormal taste sensitivity PMID: 19244541 
Trpm5tm1Sdmk Trpm5tm1Sdmk/Trpm5tm1Sdmk
involves: C57BL/6
MGI:1861718  MP:0004213 abnormal unami taste sensitivity PMID: 15738181  16355226 
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 
Trpm5tm1Dgen Trpm5tm1Dgen/Trpm5tm1Dgen
involves: 129P2/OlaHsd * C57BL/6
MGI:1861718  MP:0002169 no abnormal phenotype detected

REFERENCES

1. Bezençon C, le Coutre J, Damak S. (2007) Taste-signaling proteins are coexpressed in solitary intestinal epithelial cells. Chem. Senses32 (1): 41-9. [PMID:17030556]

2. Brixel LR, Monteilh-Zoller MK, Ingenbrandt CS, Fleig A, Penner R, Enklaar T, Zabel BU, Prawitt D. (2010) TRPM5 regulates glucose-stimulated insulin secretion. Pflugers Arch.460 (1): 69-76. [PMID:20393858]

3. Colsoul B, Schraenen A, Lemaire K, Quintens R, Van Lommel L, Segal A, Owsianik G, Talavera K, Voets T, Margolskee RF et al.. (2010) Loss of high-frequency glucose-induced Ca2+ oscillations in pancreatic islets correlates with impaired glucose tolerance in Trpm5-/- mice. Proc. Natl. Acad. Sci. U.S.A.107 (11): 5208-13. [PMID:20194741]

4. Damak S, Rong M, Yasumatsu K, Kokrashvili Z, Pérez CA, Shigemura N, Yoshida R, Mosinger B, Glendinning JI, Ninomiya Y, Margolskee RF. (2006) Trpm5 null mice respond to bitter, sweet, and umami compounds. Chem. Senses31 (3): 253-64. [PMID:16436689]

5. Enklaar T, Esswein M, Oswald M, Hilbert K, Winterpacht A, Higgins M, Zabel B, Prawitt D. (2000) Mtr1, a novel biallelically expressed gene in the center of the mouse distal chromosome 7 imprinting cluster, is a member of the Trp gene family. Genomics67 (2): 179-87. [PMID:10903843]

6. 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]

7. Hansen A, Finger TE. (2008) Is TrpM5 a reliable marker for chemosensory cells? Multiple types of microvillous cells in the main olfactory epithelium of mice. BMC Neurosci9: 115. [PMID:19055837]

8. 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]

9. Huang YA, Roper SD. (2010) Intracellular Ca(2+) and TRPM5-mediated membrane depolarization produce ATP secretion from taste receptor cells. J. Physiol. (Lond.)588 (Pt 13): 2343-50. [PMID:20498227]

10. Kim YS, Kang E, Makino Y, Park S, Shin JH, Song H, Launay P, Linden DJ. (2013) Characterizing the conductance underlying depolarization-induced slow current in cerebellar Purkinje cells. J. Neurophysiol.109 (4): 1174-81. [PMID:23197456]

11. Lin W, Ezekwe Jr EA, Zhao Z, Liman ER, Restrepo D. (2008) TRPM5-expressing microvillous cells in the main olfactory epithelium. BMC Neurosci9: 114. [PMID:19025635]

12. Lin W, Margolskee R, Donnert G, Hell SW, Restrepo D. (2007) Olfactory neurons expressing transient receptor potential channel M5 (TRPM5) are involved in sensing semiochemicals. Proc. Natl. Acad. Sci. U.S.A.104 (7): 2471-6. [PMID:17267604]

13. Lin W, Ogura T, Margolskee RF, Finger TE, Restrepo D. (2008) TRPM5-expressing solitary chemosensory cells respond to odorous irritants. J. Neurophysiol.99 (3): 1451-60. [PMID:18160424]

14. Liu D, Liman ER. (2003) Intracellular Ca2+ and the phospholipid PIP2 regulate the taste transduction ion channel TRPM5. Proc. Natl. Acad. Sci. U.S.A.100 (25): 15160-5. [PMID:14657398]

15. Liu D, Zhang Z, Liman ER. (2005) Extracellular acid block and acid-enhanced inactivation of the Ca2+-activated cation channel TRPM5 involve residues in the S3-S4 and S5-S6 extracellular domains. J. Biol. Chem.280 (21): 20691-9. [PMID:15731110]

16. Liu P, Shah BP, Croasdell S, Gilbertson TA. (2011) Transient receptor potential channel type M5 is essential for fat taste. J. Neurosci.31 (23): 8634-42. [PMID:21653867]

17. Majeed Y, Bahnasi Y, Seymour VA, Wilson LA, Milligan CJ, Agarwal AK, Sukumar P, Naylor J, Beech DJ. (2011) Rapid and contrasting effects of rosiglitazone on transient receptor potential TRPM3 and TRPC5 channels. Mol. Pharmacol.79 (6): 1023-30. [PMID:21406603]

18. Mitrovic S, Nogueira C, Cantero-Recasens G, Kiefer K, Fernández-Fernández JM, Popoff JF, Casano L, Bard FA, Gomez R, Valverde MA et al.. (2013) TRPM5-mediated calcium uptake regulates mucin secretion from human colon goblet cells. Elife2: e00658. [PMID:23741618]

19. 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]

20. 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]

21. Oike H, Wakamori M, Mori Y, Nakanishi H, Taguchi R, Misaka T, Matsumoto I, Abe K. (2006) Arachidonic acid can function as a signaling modulator by activating the TRPM5 cation channel in taste receptor cells. Biochim. Biophys. Acta1761 (9): 1078-84. [PMID:16935556]

22. Perez CA, Huang L, Rong M, Kozak JA, Preuss AK, Zhang H, Max M, Margolskee RF. (2002) A transient receptor potential channel expressed in taste receptor cells. Nat. Neurosci.5 (11): 1169-76. [PMID:12368808]

23. Prawitt D, Enklaar T, Klemm G, Gärtner B, Spangenberg C, Winterpacht A, Higgins M, Pelletier J, Zabel B. (2000) Identification and characterization of MTR1, a novel gene with homology to melastatin (MLSN1) and the trp gene family located in the BWS-WT2 critical region on chromosome 11p15.5 and showing allele-specific expression. Hum. Mol. Genet.9 (2): 203-16. [PMID:10607831]

24. Prawitt D, Monteilh-Zoller MK, Brixel L, Spangenberg C, Zabel B, Fleig A, Penner R. (2003) TRPM5 is a transient Ca2+-activated cation channel responding to rapid changes in [Ca2+]i. Proc. Natl. Acad. Sci. U.S.A.100 (25): 15166-71. [PMID:14634208]

25. Talavera K, Yasumatsu K, Voets T, Droogmans G, Shigemura N, Ninomiya Y, Margolskee RF, Nilius B. (2005) Heat activation of TRPM5 underlies thermal sensitivity of sweet taste. Nature438 (7070): 1022-5. [PMID:16355226]

26. Teruyama R, Sakuraba M, Kurotaki H, Armstrong WE. (2011) Transient receptor potential channel m4 and m5 in magnocellular cells in rat supraoptic and paraventricular nuclei. J. Neuroendocrinol.23 (12): 1204-13. [PMID:21848647]

27. Tizzano M, Gulbransen BD, Vandenbeuch A, Clapp TR, Herman JP, Sibhatu HM, Churchill ME, Silver WL, Kinnamon SC, Finger TE. (2010) Nasal chemosensory cells use bitter taste signaling to detect irritants and bacterial signals. Proc. Natl. Acad. Sci. U.S.A.107 (7): 3210-5. [PMID:20133764]

28. Ullrich ND, Voets T, Prenen J, Vennekens R, Talavera K, Droogmans G, Nilius B. (2005) Comparison of functional properties of the Ca2+-activated cation channels TRPM4 and TRPM5 from mice. Cell Calcium37 (3): 267-78. [PMID:15670874]

29. Zhang Y, Hoon MA, Chandrashekar J, Mueller KL, Cook B, Wu D, Zuker CS, Ryba NJ. (2003) Coding of sweet, bitter, and umami tastes: different receptor cells sharing similar signaling pathways. Cell112 (3): 293-301. [PMID:12581520]

30. Zhang Z, Zhao Z, Margolskee R, Liman E. (2007) The transduction channel TRPM5 is gated by intracellular calcium in taste cells. J. Neurosci.27 (21): 5777-86. [PMID:17522321]

To cite this database page, please use the following:

Dipayan Chaudhuri, David E. Clapham.
Transient Receptor Potential channels: TRPM5. Last modified on 30/01/2014. Accessed on 18/09/2014. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=497.

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