TRPM3 | Transient Receptor Potential channels | IUPHAR/BPS Guide to PHARMACOLOGY

TRPM3

Target id: 495

Nomenclature: TRPM3

Family: Transient Receptor Potential channels

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   GtoImmuPdb view: OFF :     Currently no data for TRPM3 in GtoImmuPdb

Gene and Protein Information
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 6 0 1554 9q21.11 TRPM3 transient receptor potential cation channel subfamily M member 3 3,6,9
Mouse 6 1 1709 19 B Trpm3 transient receptor potential cation channel, subfamily M, member 3 12
Rat 6 0 1721 1q51 Trpm3 transient receptor potential cation channel, subfamily M, member 3
Previous and Unofficial Names
LTRPC3 | MLSN2 | GON-2 | transient receptor potential cation channel
Database Links
CATH/Gene3D
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
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 12,18
Functional Characteristics
TRPM31235: γ = 83 pS (Na+ current), 65 pS (Ca2+ current); conducts mono and di-valent cations non-selectively (PCa/PNa = 1.6) TRPM3α1: selective for monovalent cations (PCa/PCs~0.1);
TRPM3α2: conducts mono- and di-valent cations non-selectively (PCa/PCs = 1–10);
Outwardly rectifying (magnitude varies between spice variants)
Ion Selectivity and Conductance
Species:  Human
Rank order:  Cs+ = Ca2+ > Ca2+ [73.0 - 133.0 pS]
References:  3
Ion Selectivity and Conductance Comments
Listed conductance is for TRPM31325 variant. Selectivity and conductance is heavily dependent upon splice variant and conditions [3-4,12].
Voltage Dependence
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -61.0 20.0 – 100.0 4 HEK 293 cells. Human
Inactivation  - -
Comments  TRPM31325 splice variant, activation by 10 μM D-erythrosphingosine, strong outward rectification.
Physical activators (Human)
heat (Q10 = 7.2 between 15 - 25°C; Vriens et al., 2011), hypotonic cell swelling  [13]

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
sphinganine Hs Agonist - - 2x10-5 Physiological 4
Conc range: 2x10-5 M [4]
Holding voltage: Physiological
NN-dimethyl-D-erythrosphingosine Hs Agonist - - 2x10-5 Physiological 4
Conc range: 2x10-5 M [4]
Holding voltage: Physiological
sphingosine Hs Agonist 4.9 pEC50 - Physiological 4
pEC50 4.9 (EC50 1.259x10-5 M) [4]
Holding voltage: Physiological
nifedipine Hs - - - - -
epipregnanolone sulphate Hs - - - - - 7
[7]
pregnenolone sulphate Hs - - - - - 14
[14]
Activator Comments
TRPM3 has been shown to be constitutively open [3-4,6,12]. Also activated by hypotonic cell swelling [3]. Activation by store depletion was initially reported [6] but is disputed [3].
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
2-APB Hs Antagonist - - 1x10-4 Physiological 17
Conc range: 1x10-4 M [17]
Holding voltage: Physiological
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
Mg2+ Mm Antagonist - - 9x10-3 -80.0 – 80.0 12
Conc range: 9x10-3 M [12]
Holding voltage: -80.0 – 80.0 mV
Gd3+ Hs Antagonist - - 1x10-4 -80.0 – 80.0 3,6
Conc range: 1x10-4 M [3,6]
Holding voltage: -80.0 – 80.0 mV
La3+ Hs Antagonist - - 1x10-4 Physiological 3,6
Conc range: 1x10-4 M [3,6]
Holding voltage: Physiological
rosiglitazone Hs - - - - - 8
[8]
extracellular Na+ Hs - - - - -
TRPM3α2 only
mefenamic acid Hs - - - - - 5
[5]
troglitazone Hs - - - - -
pioglitazone Hs - - - - - 8
independent of PPAR-γ [8]
View species-specific channel blocker tables
Channel Blocker Comments
Extracellular monovalent cations reduced (Na+>K+) outward currents through TRPM3α2 (short pore) but not through TRPM3α1 (long pore). Extracellular divalent cations reduced (Ca2+>Mg2+) outward currents through both TRPM3α1 and TRPM3α2 [12].
Tissue Distribution
Kidney, brain, pulmonary endothelium, cultured trigeminal neurones, neuroblastoma cells, liver, pancreas, ovaries, testes, spinal cord, iris, retinal pigmented cells.
Species:  Human
Technique:  RT-PCR, Immunocytochemistry, Northern Blot, Western Blot.
References:  1-3,6,10,15-16
Brain (dentate gyrus, intermediate lateral septal nuclei, indusium giriseum, tenia tecta, epithelium of choroid plexus).
Species:  Mouse
Technique:  In situ hybridisation, Western Blot.
References:  12
Functional Assays
Two-electrode voltage clamp, patch-clamp (whole-cell and single-channel recordings).
Species:  Human
Tissue:  HEK 293 cells.
Response measured:  Constitutively active current, responses to cell swelling, activation by ligands.
References:  3,6
Physiological Functions
Probable role in osmosensation and renal Ca2+ homeostasis, mechanosensor, cation homeostasis in cerebrospinal fluid.
Species:  Human
Tissue:  Kidney, Brain.
References:  3,6
Clinically-Relevant Mutations and Pathophysiology
Disease:  Amyotrophic lateral sclerosis with frontotemporal dementia
Comments: 
References:  6,11
Disease:  Cataract 26, multiple types; CTRCT26
OMIM: 605749
Comments: 
References:  6,11
Disease:  Hemophagocytic lymphohistiocytosis
Synonyms: Hemophagocytic syndrome [Orphanet: ORPHA158032]
Disease Ontology: DOID:0050120
OMIM: 603552
Orphanet: ORPHA158032
Comments: 
References:  6,11
Disease:  Nephronophthisis 2; NPHP2
Synonyms: Nephronophthisis [Disease Ontology: DOID:12712]
Disease Ontology: DOID:12712
OMIM: 602088
Comments: 
References:  6,11

References

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1. Bollimuntha S, Ebadi M, Singh BB. (2006) TRPC1 protects human SH-SY5Y cells against salsolinol-induced cytotoxicity by inhibiting apoptosis. Brain Res., 1099 (1): 141-9. [PMID:16765919]

2. Fantozzi I, Zhang S, Platoshyn O, Remillard CV, Cowling RT, Yuan JX. (2003) Hypoxia increases AP-1 binding activity by enhancing capacitative Ca2+ entry in human pulmonary artery endothelial cells. Am. J. Physiol. Lung Cell Mol. Physiol., 285 (6): L1233-45. [PMID:12909593]

3. Grimm C, Kraft R, Sauerbruch S, Schultz G, Harteneck C. (2003) Molecular and functional characterization of the melastatin-related cation channel TRPM3. J. Biol. Chem., 278 (24): 21493-501. [PMID:12672799]

4. Grimm C, Kraft R, Schultz G, Harteneck C. (2005) Activation of the melastatin-related cation channel TRPM3 by D-erythro-sphingosine [corrected]. Mol. Pharmacol., 67 (3): 798-805. [PMID:15550678]

5. Klose C, Straub I, Riehle M, Ranta F, Krautwurst D, Ullrich S, Meyerhof W, Harteneck C. (2011) Fenamates as TRP channel blockers: mefenamic acid selectively blocks TRPM3. Br. J. Pharmacol., 162 (8): 1757-69. [PMID:21198543]

6. Lee N, Chen J, Sun L, Wu S, Gray KR, Rich A, Huang M, Lin JH, Feder JN, Janovitz EB, Levesque PC, Blanar MA. (2003) Expression and characterization of human transient receptor potential melastatin 3 (hTRPM3). J. Biol. Chem., 278 (23): 20890-7. [PMID:12672827]

7. Majeed Y, Agarwal AK, Naylor J, Seymour VA, Jiang S, Muraki K, Fishwick CW, Beech DJ. (2010) Cis-isomerism and other chemical requirements of steroidal agonists and partial agonists acting at TRPM3 channels. Br. J. Pharmacol., 161 (2): 430-41. [PMID:20735426]

8. 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]

9. Nagase T, Kikuno R, Nakayama M, Hirosawa M, Ohara O. (2000) Prediction of the coding sequences of unidentified human genes. XVIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. DNA Res., 7 (4): 273-81. [PMID:10997877]

10. Nealen ML, Gold MS, Thut PD, Caterina MJ. (2003) TRPM8 mRNA is expressed in a subset of cold-responsive trigeminal neurons from rat. J. Neurophysiol., 90 (1): 515-20. [PMID:12634279]

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

12. Oberwinkler J, Lis A, Giehl KM, Flockerzi V, Philipp SE. (2005) Alternative splicing switches the divalent cation selectivity of TRPM3 channels. J. Biol. Chem., 280 (23): 22540-8. [PMID:15824111]

13. Vriens J, Owsianik G, Hofmann T, Philipp SE, Stab J, Chen X, Benoit M, Xue F, Janssens A, Kerselaers S et al.. (2011) TRPM3 is a nociceptor channel involved in the detection of noxious heat. Neuron, 70 (3): 482-94. [PMID:21555074]

14. Wagner TF, Loch S, Lambert S, Straub I, Mannebach S, Mathar I, Düfer M, Lis A, Flockerzi V, Philipp SE et al.. (2008) Transient receptor potential M3 channels are ionotropic steroid receptors in pancreatic beta cells. Nat. Cell Biol., 10 (12): 1421-30. [PMID:18978782]

15. Wistow G, Bernstein SL, Ray S, Wyatt MK, Behal A, Touchman JW, Bouffard G, Smith D, Peterson K. (2002) Expressed sequence tag analysis of adult human iris for the NEIBank Project: steroid-response factors and similarities with retinal pigment epithelium. Mol. Vis., 8: 185-95. [PMID:12107412]

16. Wistow G, Bernstein SL, Wyatt MK, Fariss RN, Behal A, Touchman JW, Bouffard G, Smith D, Peterson K. (2002) Expressed sequence tag analysis of human RPE/choroid for the NEIBank Project: over 6000 non-redundant transcripts, novel genes and splice variants. Mol. Vis., 8: 205-20. [PMID:12107410]

17. Xu SZ, Zeng F, Boulay G, Grimm C, Harteneck C, Beech DJ. (2005) Block of TRPC5 channels by 2-aminoethoxydiphenyl borate: a differential, extracellular and voltage-dependent effect. Br. J. Pharmacol., 145 (4): 405-14. [PMID:15806115]

18. Yap KL, Kim J, Truong K, Sherman M, Yuan T, Ikura M. (2000) Calmodulin target database. J. Struct. Funct. Genomics, 1 (1): 8-14. [PMID:12836676]

Contributors

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How to cite this page

David E. Clapham, Bernd Nilius, Grzegorz Owsianik.
Transient Receptor Potential channels: TRPM3. Last modified on 24/04/2017. Accessed on 16/11/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=495.