TRPC3 | Transient Receptor Potential channels | IUPHAR/BPS Guide to PHARMACOLOGY

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target has curated data in GtoImmuPdb

Target id: 488

Nomenclature: TRPC3

Family: Transient Receptor Potential channels

Gene and Protein Information
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 6 1 848 4q27 TRPC3 transient receptor potential cation channel subfamily C member 3 38
Mouse 6 1 836 3 B Trpc3 transient receptor potential cation channel 23
Rat 6 1 736 2q25 Trpc3 transient receptor potential cation channel 24
Previous and Unofficial Names
TRP3 [38] | short transient receptor potential channel 3 | transient receptor protein 3 | trp-related protein 3 | transient receptor potential cation channel
Database Links
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
RefSeq Nucleotide
RefSeq Protein
Associated Proteins
Heteromeric Pore-forming Subunits
Name References
TRPC1 36-37
Auxiliary Subunits
Name References
Not determined
Other Associated Proteins
Name References
VAMP2 32
MxA 19
Sodium/calcium exchanger 1 29
syntaxin 3
FKBP prolyl isomerase 1A 32
C-terminal tail-truncated TRPP2 22
IP3R1 1
GluD2 14
Functional Characteristics
γ = 66 pS; conducts mono and di-valent cations non-selectively (PCa/PNa = 1.6); monovalent cation current suppressed by extracellular Ca2+; dual (inward and outward) rectification
Ion Selectivity and Conductance
Species:  Human
Rank order:  Ca2+ > Na+ [66.0 pS]
References:  39
Ion Selectivity and Conductance Comments
Non-selective cation channel.
Chemical activators (Human)

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

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
OAG Hs Agonist - - 1x10-4 -60.0 10
Conc range: 1x10-4 M [10]
Holding voltage: -60.0 mV
pyrazolopyrimidine 4n Hs Activation 7.7 pEC50 - - 26
pEC50 7.7 (EC50 1.9x10-8 M) [26]
GSK1702934A Hs Agonist 7.1 pEC50 - - 35
pEC50 7.1 (EC50 8x10-8 M) [35]
Description: Activation of hTRPC3-mediated currents in HEK293 cells in whole-cell patch-clamp experiments.
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
norgestimate Hs - 5.5 pKi - - 21
pKi 5.5 (Ki 3x10-6 M) [21]
Description: Norgestimate-induced inhibition of hTRPC3-mediated Ca2+ entry in transfected CHO cells stimulated with the OAG diacylglycerol analog.
Gd3+ Hs Antagonist 7.0 pEC50 - -60.0 7
pEC50 7.0 (EC50 1x10-7 M) [7]
Holding voltage: -60.0 mV
GSK2833503A Hs - 7.7 pIC50 - 80.0 31
pIC50 7.7 (IC50 2.1x10-8 M) [31]
Holding voltage: 80.0 mV
Description: Measuring whole-cell current by patch-clamp in HEK cells expressing hTRPC3 with cation flux activated by OAG.
GSK417651A Hs Antagonist 7.1 pIC50 - - 34
pIC50 7.1 (IC50 8x10-8 M) [34]
Description: Inhibition of recombinant hTRPC3-mediated, carbachol-stimulated Ca2+/Na+ influx in HEK293-MSRII cells assessed by FLIPR assay.
SAR7334 Hs - 6.6 pIC50 - - 20
pIC50 6.6 (IC50 2.82x10-7 M) [20]
BTP2 Hs Antagonist 6.5 pIC50 - -80.0 9
pIC50 6.5 (IC50 3x10-7 M) [9]
Holding voltage: -80.0 mV
Pyr3 Hs - 6.2 pIC50 - - 15
pIC50 6.2 (IC50 7x10-7 M) [15]
Pyr10 Hs Antagonist 6.1 pIC50 - - 30
pIC50 6.1 (IC50 7.2x10-7 M) [30]
Description: Measuring blockade of TRPC3-mediated receptor operated Ca2+ entry in vitro.
SH045 Hs - 6.1 pIC50 - - 11
pIC50 6.1 (IC50 8.4x10-7 M) [11]
Description: Measuring inhibition of calcium flux in HEK293 cells expressing hTRPC3, in a FLIPR assay.
La3+ Hs Antagonist 5.4 pIC50 - -60.0 7
pIC50 5.4 (IC50 4x10-6 M) [7]
Holding voltage: -60.0 mV
clemizole Hs - 5.0 pIC50 - - 28
pIC50 5.0 (IC50 9.1x10-6 M) [28]
2-APB Hs Antagonist 5.0 pIC50 - Physiological 18
pIC50 5.0 (IC50 1x10-5 M) [18]
Holding voltage: Physiological
SKF96365 Hs - - - - -
ACAA Hs - - - - -
Ni2+ Hs - - - - -
KB-R7943 Hs - - - - -
Immunopharmacology Comments
Expressed on B cells, T cells, neutrophils and monocytes/macrophages [25].
Cell Type Associations
Immuno Cell Type:  T cells
Comment:  TRPC channels (e.g. TRPC3, TRPC5, TRPC6) are involved in TCR signalling, proliferation and autoimmune suppression.
References:  25
Immuno Cell Type:  Granulocytes
Comment:  TRPC channels (e.g. TRPC3, TRPC6) are involved in chemotaxis, LTC4 secretion and PAF signalling
References:  25
Immuno Cell Type:  Macrophages & monocytes
Comment:  TRPC channels (e.g. TRPC3, TRPC6) are involved in macrophage activation.
References:  25
Tissue Distribution
Pituitary gland > brain, heart, lung, dorsal root ganglia.
Species:  Human
Technique:  RT-PCR
References:  27
Brain, thymus, spleen, liver, kidney, ovary, dorsal root ganglion, skin, skeletal and smooth muscle, retina, heart, lung, testis, innear ear.
Species:  Mouse
Technique:  RT-PCR, northern blot
References:  6,12-13,33
Functional Assays
Suppression of oxidant-induced membrane currents by expression of a dominant negative fragment of hTRPC3.
Species:  Human
Tissue:  Aortic endothelial cells.
Response measured:  The tBHP-induced membrane depolarization was reduced in N-terminal fragment of hTrp3-transfected endothelial cells.
References:  2
Activation of TrkB and PLC leads to a TRPC3-dependent cation influx in SNS neurones.
Species:  Rat
Tissue:  Brain.
Response measured:  BDNF-induced cation influx mediated by TRPC3 channel.
References:  16
TRPC3 contributes to the BDNF-induced chemo-attractive turning.
Species:  Rat
Tissue:  Cerebellum
Response measured: 
References:  17
Physiological Functions
TRPC3 null mice exhibit an impaired walking behavior.
Species:  Mouse
Tissue:  Brain
References:  8
A point mutation in TRPC3 causes cerebellar ataxia in moonwalker mice.
Species:  Mouse
Tissue:  Brain
References:  4
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Trpc3tm1.1Akon Trpc3tm1.1Akon/Trpc3tm1.1Akon
involves: 129S/SvEv * 129S4/SvJaeSor
MGI:109526  MP:0002910 abnormal excitatory postsynaptic currents PMID: 18701065 
Trpc3tm1.1Akon Trpc3tm1.1Akon/Trpc3tm1.1Akon
involves: 129S/SvEv * 129S4/SvJaeSor
MGI:109526  MP:0001406 abnormal gait PMID: 18701065 
Trpc3+|Trpc3Mwk Trpc3Mwk/Trpc3+
involves: BALB/cAnN * C3H/HeH
MGI:109526  MP:0001406 abnormal gait PMID: 19351902 
Trpc3+|Trpc3Mwk Trpc3Mwk/Trpc3+
involves: BALB/cAnN * C3H/HeH
MGI:109526  MP:0002272 abnormal nervous system electrophysiology PMID: 19351902 
Trpc3+|Trpc3Mwk Trpc3Mwk/Trpc3+
involves: BALB/cAnN * C3H/HeH
MGI:109526  MP:0008572 abnormal Purkinje cell dendrite morphology PMID: 19351902 
Trpc3+|Trpc3Mwk Trpc3Mwk/Trpc3+
involves: BALB/cAnN * C3H/HeH
MGI:109526  MP:0000877 abnormal Purkinje cell morphology PMID: 19351902 
Trpc3+|Trpc3Mwk Trpc3Mwk/Trpc3+
involves: BALB/cAnN * C3H/HeH
MGI:109526  MP:0001265 decreased body size PMID: 19351902 
Trpc3+|Trpc3Mwk Trpc3Mwk/Trpc3+
involves: BALB/cAnN * C3H/HeH
MGI:109526  MP:0000880 decreased Purkinje cell number PMID: 19351902 
Trpc3+|Trpc3Mwk Trpc3Mwk/Trpc3+
involves: BALB/cAnN * C3H/HeH
MGI:109526  MP:0001525 impaired balance PMID: 19351902 
Trpc3tm1.1Akon Trpc3tm1.1Akon/Trpc3tm1.1Akon
involves: 129S/SvEv * 129S4/SvJaeSor
MGI:109526  MP:0001524 impaired limb coordination PMID: 18701065 
Trpc3Mwk Trpc3Mwk/Trpc3Mwk
involves: BALB/cAnN * C3H/HeH
MGI:109526  MP:0002083 premature death PMID: 19351902 


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1. Adebiyi A, Zhao G, Narayanan D, Thomas-Gatewood CM, Bannister JP, Jaggar JH. (2010) Isoform-selective physical coupling of TRPC3 channels to IP3 receptors in smooth muscle cells regulates arterial contractility. Circ. Res., 106 (10): 1603-12. [PMID:20378853]

2. Balzer M, Lintschinger B, Groschner K. (1999) Evidence for a role of Trp proteins in the oxidative stress-induced membrane conductances of porcine aortic endothelial cells. Cardiovasc. Res., 42 (2): 543-9. [PMID:10533589]

3. Bandyopadhyay BC, Swaim WD, Liu X, Redman RS, Patterson RL, Ambudkar IS. (2005) Apical localization of a functional TRPC3/TRPC6-Ca2+-signaling complex in polarized epithelial cells. Role in apical Ca2+ influx. J. Biol. Chem., 280 (13): 12908-16. [PMID:15623527]

4. Becker EB, Oliver PL, Glitsch MD, Banks GT, Achilli F, Hardy A, Nolan PM, Fisher EM, Davies KE. (2009) A point mutation in TRPC3 causes abnormal Purkinje cell development and cerebellar ataxia in moonwalker mice. Proc. Natl. Acad. Sci. U.S.A., 106 (16): 6706-11. [PMID:19351902]

5. Dietrich A, Kalwa H, Rost BR, Gudermann T. (2005) The diacylgylcerol-sensitive TRPC3/6/7 subfamily of cation channels: functional characterization and physiological relevance. Pflugers Arch., 451 (1): 72-80. [PMID:15971081]

6. Gilliam JC, Wensel TG. (2011) TRP channel gene expression in the mouse retina. Vision Res., 51 (23-24): 2440-52. [PMID:22037305]

7. Halaszovich CR, Zitt C, Jungling E, Luckhoff A. (2000) Inhibition of TRP3 channels by lanthanides. Block from the cytosolic side of the plasma membrane. J. Biol. Chem., 275 (48): 37423-8. [PMID:10970899]

8. Hartmann J, Dragicevic E, Adelsberger H, Henning HA, Sumser M, Abramowitz J, Blum R, Dietrich A, Freichel M, Flockerzi V et al.. (2008) TRPC3 channels are required for synaptic transmission and motor coordination. Neuron, 59 (3): 392-8. [PMID:18701065]

9. He LP, Hewavitharana T, Soboloff J, Spassova MA, Gill DL. (2005) A functional link between store-operated and TRPC channels revealed by the 3,5-bis(trifluoromethyl)pyrazole derivative, BTP2. J. Biol. Chem., 280 (12): 10997-1006. [PMID:15647288]

10. Hofmann T, Obukhov AG, Schaefer M, Harteneck C, Gudermann T, Schultz G. (1999) Direct activation of human TRPC6 and TRPC3 channels by diacylglycerol. Nature, 397 (6716): 259-63. [PMID:9930701]

11. Häfner S, Burg F, Kannler M, Urban N, Mayer P, Dietrich A, Trauner D, Broichhagen J, Schaefer M. (2018) A (+)-Larixol Congener with High Affinity and Subtype Selectivity toward TRPC6. ChemMedChem, 13 (10): 1028-1035. [PMID:29522264]

12. 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]

13. 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]

14. Kato AS, Knierman MD, Siuda ER, Isaac JT, Nisenbaum ES, Bredt DS. (2012) Glutamate receptor δ2 associates with metabotropic glutamate receptor 1 (mGluR1), protein kinase Cγ, and canonical transient receptor potential 3 and regulates mGluR1-mediated synaptic transmission in cerebellar Purkinje neurons. J. Neurosci., 32 (44): 15296-308. [PMID:23115168]

15. Kiyonaka S, Kato K, Nishida M, Mio K, Numaga T, Sawaguchi Y, Yoshida T, Wakamori M, Mori E, Numata T et al.. (2009) Selective and direct inhibition of TRPC3 channels underlies biological activities of a pyrazole compound. Proc. Natl. Acad. Sci. U.S.A., 106 (13): 5400-5. [PMID:19289841]

16. Li HS, Xu XZ, Montell C. (1999) Activation of a TRPC3-dependent cation current through the neurotrophin BDNF. Neuron, 24 (1): 261-73. [PMID:10677043]

17. Li Y, Jia YC, Cui K, Li N, Zheng ZY, Wang YZ, Yuan XB. (2005) Essential role of TRPC channels in the guidance of nerve growth cones by brain-derived neurotrophic factor. Nature, 434 (7035): 894-8. [PMID:15758952]

18. Lievremont JP, Bird GS, Putney Jr JW. (2005) Mechanism of inhibition of TRPC cation channels by 2-aminoethoxydiphenylborane. Mol. Pharmacol., 68 (3): 758-62. [PMID:15933213]

19. Lussier MP, Cayouette S, Lepage PK, Bernier CL, Francoeur N, St-Hilaire M, Pinard M, Boulay G. (2005) MxA, a member of the dynamin superfamily, interacts with the ankyrin-like repeat domain of TRPC. J. Biol. Chem., 280 (19): 19393-400. [PMID:15757897]

20. Maier T, Follmann M, Hessler G, Kleemann HW, Hachtel S, Fuchs B, Weissmann N, Linz W, Schmidt T, Löhn M et al.. (2015) Discovery and pharmacological characterization of a novel potent inhibitor of diacylglycerol-sensitive TRPC cation channels. Br. J. Pharmacol., 172 (14): 3650-60. [PMID:25847402]

21. Miehe S, Crause P, Schmidt T, Löhn M, Kleemann HW, Licher T, Dittrich W, Rütten H, Strübing C. (2012) Inhibition of diacylglycerol-sensitive TRPC channels by synthetic and natural steroids. PLoS ONE, 7 (4): e35393. [PMID:22530015]

22. Miyagi K, Kiyonaka S, Yamada K, Miki T, Mori E, Kato K, Numata T, Sawaguchi Y, Numaga T, Kimura T et al.. (2009) A pathogenic C terminus-truncated polycystin-2 mutant enhances receptor-activated Ca2+ entry via association with TRPC3 and TRPC7. J. Biol. Chem., 284 (49): 34400-12. [PMID:19812035]

23. Mori Y, Takada N, Okada T, Wakamori M, Imoto K, Wanifuchi H, Oka H, Oba A, Ikenaka K, Kurosaki T. (1998) Differential distribution of TRP Ca2+ channel isoforms in mouse brain. Neuroreport, 9 (3): 507-15. [PMID:9512398]

24. Ohki G, Miyoshi T, Murata M, Ishibashi K, Imai M, Suzuki M. (2000) A calcium-activated cation current by an alternatively spliced form of Trp3 in the heart. J. Biol. Chem., 275 (50): 39055-60. [PMID:10984475]

25. Parenti A, De Logu F, Geppetti P, Benemei S. (2016) What is the evidence for the role of TRP channels in inflammatory and immune cells?. Br. J. Pharmacol., 173 (6): 953-69. [PMID:26603538]

26. Qu C, Ding M, Zhu Y, Lu Y, Du J, Miller M, Tian J, Zhu J, Xu J, Wen M et al.. (2017) Pyrazolopyrimidines as Potent Stimulators for Transient Receptor Potential Canonical 3/6/7 Channels. J. Med. Chem., 60 (11): 4680-4692. [PMID:28395140]

27. Riccio A, Medhurst AD, Mattei C, Kelsell RE, Calver AR, Randall AD, Benham CD, Pangalos MN. (2002) mRNA distribution analysis of human TRPC family in CNS and peripheral tissues. Brain Res. Mol. Brain Res., 109 (1-2): 95-104. [PMID:12531519]

28. Richter JM, Schaefer M, Hill K. (2014) Clemizole hydrochloride is a novel and potent inhibitor of transient receptor potential channel TRPC5. Mol. Pharmacol., 86 (5): 514-21. [PMID:25140002]

29. Rosker C, Graziani A, Lukas M, Eder P, Zhu MX, Romanin C, Groschner K. (2004) Ca(2+) signaling by TRPC3 involves Na(+) entry and local coupling to the Na(+)/Ca(2+) exchanger. J. Biol. Chem., 279 (14): 13696-704. [PMID:14736881]

30. Schleifer H, Doleschal B, Lichtenegger M, Oppenrieder R, Derler I, Frischauf I, Glasnov TN, Kappe CO, Romanin C, Groschner K. (2012) Novel pyrazole compounds for pharmacological discrimination between receptor-operated and store-operated Ca(2+) entry pathways. Br. J. Pharmacol., 167 (8): 1712-22. [PMID:22862290]

31. Seo K, Rainer PP, Shalkey Hahn V, Lee DI, Jo SH, Andersen A, Liu T, Xu X, Willette RN, Lepore JJ et al.. (2014) Combined TRPC3 and TRPC6 blockade by selective small-molecule or genetic deletion inhibits pathological cardiac hypertrophy. Proc. Natl. Acad. Sci. U.S.A., 111 (4): 1551-6. [PMID:24453217]

32. Sinkins WG, Goel M, Estacion M, Schilling WP. (2004) Association of immunophilins with mammalian TRPC channels. J. Biol. Chem., 279 (33): 34521-9. [PMID:15199065]

33. Takumida M, Anniko M. (2009) Expression of canonical transient receptor potential channel (TRPC) 1-7 in the mouse inner ear. Acta Otolaryngol., 129 (12): 1351-8. [PMID:19922081]

34. Washburn DG, Holt DA, Dodson J, McAtee JJ, Terrell LR, Barton L, Manns S, Waszkiewicz A, Pritchard C, Gillie DJ et al.. (2013) The discovery of potent blockers of the canonical transient receptor channels, TRPC3 and TRPC6, based on an anilino-thiazole pharmacophore. Bioorg. Med. Chem. Lett., 23 (17): 4979-84. [PMID:23886683]

35. Xu X, Lozinskaya I, Costell M, Lin Z, Ball JA, Bernard R, Behm DJ, Marino JP, Schnackenberg CG. (2013) Characterization of Small Molecule TRPC3 and TRPC6 agonist and Antagonists. Biophys. J, 104 (2): 454a Meeting abstract. DOI: 10.1016/j.bpj.2012.11.2513

36. Yuan JP, Zeng W, Huang GN, Worley PF, Muallem S. (2007) STIM1 heteromultimerizes TRPC channels to determine their function as store-operated channels. Nat. Cell Biol., 9 (6): 636-45. [PMID:17486119]

37. Zagranichnaya TK, Wu X, Villereal ML. (2005) Endogenous TRPC1, TRPC3, and TRPC7 proteins combine to form native store-operated channels in HEK-293 cells. J. Biol. Chem., 280 (33): 29559-69. [PMID:15972814]

38. Zhu X, Jiang M, Peyton M, Boulay G, Hurst R, Stefani E, Birnbaumer L. (1996) trp, a novel mammalian gene family essential for agonist-activated capacitative Ca2+ entry. Cell, 85 (5): 661-71. [PMID:8646775]

39. Zitt C, Obukhov AG, Strübing C, Zobel A, Kalkbrenner F, Lückhoff A, Schultz G. (1997) Expression of TRPC3 in Chinese hamster ovary cells results in calcium-activated cation currents not related to store depletion. J. Cell Biol., 138 (6): 1333-41. [PMID:9298988]


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