TRPC1 | Transient Receptor Potential channels | IUPHAR/BPS Guide to PHARMACOLOGY

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TRPC1

Target not currently curated in GtoImmuPdb

Target id: 486

Nomenclature: TRPC1

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

Gene and Protein Information
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 6 1 759 3q22-24 TRPC1 transient receptor potential cation channel subfamily C member 1 22
Mouse 6 1 809 9 E4 Trpc1 transient receptor potential cation channel
Rat 6 1 759 8q31 Trpc1 transient receptor potential cation channel 18
Previous and Unofficial Names
TRP1 | short transient receptor potential channel 1 | transient receptor potential cation channel
Database Links
CATH/Gene3D
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Associated Proteins
Heteromeric Pore-forming Subunits
Name References
TRPC5 15
TRPC3 16
TRPC4 15
TRPP2 9,20
TRPV6 13
Auxiliary Subunits
Name References
Not determined
Other Associated Proteins
Name References
STIM1 7
IP3R 19
Homer 19
calmodulin 14
D2 receptor 6
caveolin-1 17
α1 syntrophin 12
Functional Characteristics
It is not yet clear that TRPC1 forms a homomer. It does form heteromers with TRPC4 and TRPC5
Ion Selectivity and Conductance
Species:  Human
Rank order:  Ca2+ [5.0 pS] = Cs+ [5.0 pS] = Na+ [5.0 pS]
References:  15
Chemical activators (Human)
NO-mediated cysteine S-nitrosylation
Physical activators (Human)
membrane stretch (likely direct)

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

Activator Comments
The precise activation pathway of TRPC1 containing channels remains controversial, as do the interaction partners. There is evidence that TRPC1 is involved in store-operated calcium entry, via interactions with STIM1 (reviewed in [2]), yet other researchers see no effect [4]. Recent work suggests TRPC1 may form a channel on endoplasmic and/or sarcoplasmic reticulum membranes [1,3].

When complexed with TRPC4 or TRPC5, TRPC1 is activated as a result of stimulation of Gq signalling pathways. The precise mechanism is unclear.

Low concentrations of La3+ or Gd3+ enhance TRPC1/4 or C1/5 currents. TRPC1 does not appear to be a mechanically sensitive channel [5].
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
La3+ Hs Antagonist - - 1x10-4 -70.0 15
Conc range: 1x10-4 M [15]
Holding voltage: -70.0 mV
Gd3+ Hs Antagonist - - 2x10-5 -70.0 22
Conc range: 2x10-5 M [22]
Holding voltage: -70.0 mV
2-APB Hs Antagonist - - - -70.0 15
[15]
Holding voltage: -70.0 mV
SKF96365 Hs - - - - -
GsMTx-4 Hs - - - - -
Tissue Distribution
Heart, brain, lung, liver > spleen, kidney, testes.
Species:  Rat
Technique:  Northern Blot.
References:  18
Brain (CA3 hippocampus, cerebellar Purkinje neurones).
Species:  Rat
Technique:  Immunohistochemistry
References:  15
Functional Assays
Enhances store-operated calcium entry.
Species:  Human
Tissue:  Tranfected COS cells.
Response measured:  Ca2+ levels by fluorescence videomicroscopy.
References:  21
Generates a non-selective cation current in heterologously-expressing cells, activated by G protein-coupled receptors or perhaps by membrane stretch.
Species:  Human
Tissue:  Heterologous expression, Xenopus oocytes.
Response measured:  Cation current.
References:  11,22
Physiological Functions
Contributes to slow excitatory postsynaptic potential activated by metabotropic glutamate receptors in cerebellar Purkinje neurones.
Species:  Rat
Tissue:  Cerebellar Purkinje neurones.
References:  8
May form channel in skeletal muscle sarcoplasmic reticulum.
Species:  Mouse
Tissue:  Skeletal muscle
References:  3
May contribute to relaxation of mouse aorta.
Species:  Mouse
Tissue:  Aortic endothelial and smooth muscle cells.
References:  10
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Trpc1tm1Lbi Trpc1tm1Lbi/Trpc1tm1Lbi
involves: 129S/SvEv
MGI:109528  MP:0005310 abnormal salivary gland physiology PMID: 17956991 
Trpc1tm1Lbi Trpc1tm1Lbi/Trpc1tm1Lbi
involves: 129S/SvEv
MGI:109528  MP:0000623 decreased salivation PMID: 17956991 
Trpc1tm1Lbi Trpc1tm1Lbi/Trpc1tm1Lbi
involves: 129S/SvEv * C57BL/6J
MGI:109528  MP:0001264 increased body size PMID: 17647013 
Trpc1tm1Lbi Trpc1tm1Lbi/Trpc1tm1Lbi
involves: 129S/SvEv * C57BL/6J
MGI:109528  MP:0001260 increased body weight PMID: 17647013 

References

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1. Alfonso S, Benito O, Alicia S, Angélica Z, Patricia G, Diana K, Vaca L, Luis V. (2008) Regulation of the cellular localization and function of human transient receptor potential channel 1 by other members of the TRPC family. Cell Calcium, 43 (4): 375-87. [PMID:17850866]

2. Ambudkar IS, Ong HL, Liu X, Bandyopadhyay BC, Bandyopadhyay B, Cheng KT. (2007) TRPC1: the link between functionally distinct store-operated calcium channels. Cell Calcium, 42 (2): 213-23. [PMID:17350680]

3. Berbey C, Weiss N, Legrand C, Allard B. (2009) Transient receptor potential canonical type 1 (TRPC1) operates as a sarcoplasmic reticulum calcium leak channel in skeletal muscle. J. Biol. Chem., 284 (52): 36387-94. [PMID:19875453]

4. DeHaven WI, Jones BF, Petranka JG, Smyth JT, Tomita T, Bird GS, Putney Jr JW. (2009) TRPC channels function independently of STIM1 and Orai1. J. Physiol. (Lond.), 587 (Pt 10): 2275-98. [PMID:19332491]

5. Gottlieb P, Folgering J, Maroto R, Raso A, Wood TG, Kurosky A, Bowman C, Bichet D, Patel A, Sachs F et al.. (2008) Revisiting TRPC1 and TRPC6 mechanosensitivity. Pflugers Arch., 455 (6): 1097-103. [PMID:17957383]

6. Hannan MA, Kabbani N, Paspalas CD, Levenson R. (2008) Interaction with dopamine D2 receptor enhances expression of transient receptor potential channel 1 at the cell surface. Biochim. Biophys. Acta, 1778 (4): 974-82. [PMID:18261457]

7. Huang GN, Zeng W, Kim JY, Yuan JP, Han L, Muallem S, Worley PF. (2006) STIM1 carboxyl-terminus activates native SOC, I(crac) and TRPC1 channels. Nat. Cell Biol., 8 (9): 1003-10. [PMID:16906149]

8. Kim SJ, Kim YS, Yuan JP, Petralia RS, Worley PF, Linden DJ. (2003) Activation of the TRPC1 cation channel by metabotropic glutamate receptor mGluR1. Nature, 426 (6964): 285-91. [PMID:14614461]

9. Kobori T, Smith GD, Sandford R, Edwardson JM. (2009) The transient receptor potential channels TRPP2 and TRPC1 form a heterotetramer with a 2:2 stoichiometry and an alternating subunit arrangement. J. Biol. Chem., 284 (51): 35507-13. [PMID:19850920]

10. Kochukov MY, Balasubramanian A, Noel RC, Marrelli SP. (2013) Role of TRPC1 and TRPC3 channels in contraction and relaxation of mouse thoracic aorta. J. Vasc. Res., 50 (1): 11-20. [PMID:23095462]

11. Maroto R, Raso A, Wood TG, Kurosky A, Martinac B, Hamill OP. (2005) TRPC1 forms the stretch-activated cation channel in vertebrate cells. Nat. Cell Biol., 7 (2): 179-85. [PMID:15665854]

12. Sabourin J, Lamiche C, Vandebrouck A, Magaud C, Rivet J, Cognard C, Bourmeyster N, Constantin B. (2009) Regulation of TRPC1 and TRPC4 cation channels requires an alpha1-syntrophin-dependent complex in skeletal mouse myotubes. J. Biol. Chem., 284 (52): 36248-61. [PMID:19812031]

13. Schindl R, Fritsch R, Jardin I, Frischauf I, Kahr H, Muik M, Riedl MC, Groschner K, Romanin C. (2012) Canonical transient receptor potential (TRPC) 1 acts as a negative regulator for vanilloid TRPV6-mediated Ca2+ influx. J. Biol. Chem., 287 (42): 35612-20. [PMID:22932896]

14. Singh BB, Liu X, Tang J, Zhu MX, Ambudkar IS. (2002) Calmodulin regulates Ca(2+)-dependent feedback inhibition of store-operated Ca(2+) influx by interaction with a site in the C terminus of TrpC1. Mol. Cell, 9 (4): 739-50. [PMID:11983166]

15. Strübing C, Krapivinsky G, Krapivinsky L, Clapham DE. (2001) TRPC1 and TRPC5 form a novel cation channel in mammalian brain. Neuron, 29 (3): 645-55. [PMID:11301024]

16. Strübing C, Krapivinsky G, Krapivinsky L, Clapham DE. (2003) Formation of novel TRPC channels by complex subunit interactions in embryonic brain. J. Biol. Chem., 278 (40): 39014-9. [PMID:12857742]

17. Sundivakkam PC, Kwiatek AM, Sharma TT, Minshall RD, Malik AB, Tiruppathi C. (2009) Caveolin-1 scaffold domain interacts with TRPC1 and IP3R3 to regulate Ca2+ store release-induced Ca2+ entry in endothelial cells. Am. J. Physiol., Cell Physiol., 296 (3): C403-13. [PMID:19052258]

18. Wang W, O'Connell B, Dykeman R, Sakai T, Delporte C, Swaim W, Zhu X, Birnbaumer L, Ambudkar IS. (1999) Cloning of Trp1beta isoform from rat brain: immunodetection and localization of the endogenous Trp1 protein. Am. J. Physiol., 276 (4 Pt 1): C969-79. [PMID:10199829]

19. Yuan JP, Kiselyov K, Shin DM, Chen J, Shcheynikov N, Kang SH, Dehoff MH, Schwarz MK, Seeburg PH, Muallem S et al.. (2003) Homer binds TRPC family channels and is required for gating of TRPC1 by IP3 receptors. Cell, 114 (6): 777-89. [PMID:14505576]

20. Zhang P, Luo Y, Chasan B, González-Perrett S, Montalbetti N, Timpanaro GA, Cantero Mdel R, Ramos AJ, Goldmann WH, Zhou J et al.. (2009) The multimeric structure of polycystin-2 (TRPP2): structural-functional correlates of homo- and hetero-multimers with TRPC1. Hum. Mol. Genet., 18 (7): 1238-51. [PMID:19193631]

21. 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]

22. Zitt C, Zobel A, Obukhov AG, Harteneck C, Kalkbrenner F, Lückhoff A, Schultz G. (1996) Cloning and functional expression of a human Ca2+-permeable cation channel activated by calcium store depletion. Neuron, 16 (6): 1189-96. [PMID:8663995]

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