Nomenclature: TRPC5

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 1 973 Xq23 TRPC5 transient receptor potential cation channel, subfamily C, member 5
Mouse 6 1 975 X F2 Trpc5 transient receptor potential cation channel, subfamily C, member 5
Rat 6 1 974 Xq14 Trpc5 transient receptor potential cation channel, subfamily C, member 5
Previous and Unofficial Names
TRP5
CCE2
Trrp5
short transient receptor potential channel 5
transient receptor potential cation channel, subfamily C, member 5
transient receptor protein 5
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
Associated Proteins
Heteromeric Pore-forming Subunits
Name References
TRPC1 30
TRPC3 31
Auxiliary Subunits
Name References
Not determined
Other Associated Proteins
Name References
calmodulin 25
NHERF 32
MxA 17
CaBP1 14
i3 11
D2 receptor 9
NCS-1 10
SESTD1 20
STIM1 36
Functional Characteristics
γ = 41-63 pS; conducts mono-and di-valent cations non-selectively (PCa/PNa = 1.8 – 9.5); dual rectification (inward and outward) as a homomer, outwardly rectifying when expressed with TRPC1 or TRPC4
Ion Selectivity and Conductance
Species:  Mouse
Rank order:  Ca2+ > K+ [35.0 pS] = Cs+ = Na+
References:  29-30
Voltage Dependence Comments
Obukhov and Nowycky [23] have shown voltage dependent TRPC5 currents, yet the parameters have not been fully described.
Other chemical activators (Human)
NO-mediated cysteine S-nitrosylation (disputed), potentiation by extracellular protons
Physical activators (Human)
Membrane stretch (likely indirect)
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
Gd3+ Hs - - - 1x10-4 -
Conc range: 1x10-4 M
Pb2+ Hs - - - 5x10-6 -
Conc range: 5x10-6 M
intracellular Ca2+ Hs - 6.2 pEC50 - -
pEC50 6.2 (EC50 6.35x10-7 M) at negative potentials
Ca2+ Mm Activation 6.0 pEC50 - - 1,8
pEC50 6.0 Internal calcium [1,8]
rosiglitazone Hs Activation 4.51 pEC50 - - 19
pEC50 4.51 [19]
lysophosphatidylcholine Hs - - - - -
La3+ Hs - - - - -
μM range
7,4'-dihydroxyisoflavone Hs - - - - -
genistein Hs - - - - - 33
independent of tyrosine kinase inhibition [33]
View species-specific activator tables
Activator Comments
Activated by stimulation of GPCRs coupled to Gq stimulation. Precise pathway is unclear. Also, potentiated by 10-100 μM La3+ and Gd3+ [12,29-30]. When complexed with TRPC1, a current with a unique I-V relationship is formed [30].

TRPC5 has been proposed to be activated by receptors coupled to Gαi and Gαo [11], to be potentiated by nitric oxide [35] and external protons [22], and activated by caplain cleavage [13].
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
La3+ Mm Antagonist - - 5x10-3 -60.0 12
Conc range: 5x10-3 M [12]
Holding voltage: -60.0 mV
KB-R7943 Hs Inhibition 5.86 pIC50 - - 15
pIC50 5.86 (IC50 1.38x10-6 M) [15]
progesterone Hs Inhibition 5.3 pIC50 - - 18
pIC50 5.3 [18]
ML204 Hs - ~5.0 pIC50 - - 21
pIC50 ~5.0 (IC50 ~1x10-5 M) [21]
BEL Mm Inhibition 4.97 pIC50 - - 2
pIC50 4.97 [2]
2-APB Hs Antagonist 4.7 pIC50 - -80.0 34
pIC50 4.7 (IC50 2x10-5 M) [34]
Holding voltage: -80.0 mV
Mg2+ Rn Inhibition 3.34 pIC50 - - 22
pIC50 3.34 Internal magnesium [22]
flufenamic acid Hs - - - - -
chlorpromazine Hs - - - - -
GsMTx-4 Hs - - - - -
SKF96365 Hs - - - - -
BTP2 Hs - - - - -
View species-specific channel blocker tables
Channel Blocker Comments
It is not know for any of the inhibitors whether they act as pore blockers or gating inhibitors. Lanthanum and gadolinium block the channel, as well as potentiate [12]. 10µM external ML204 completely blocks mouse TRPC5 [21]. Internal ATP has been reported to block TRPC5 [4].
Tissue Distribution
Brain, testes, kidney, uterus.
Species:  Mouse
Technique:  Northern Blot
References:  24
Hippocampus, cerebellar Purkinje neurones, mitral cells of olfactory bulb.
Species:  Mouse
Technique:  In situ hybridisation
References:  26
Brain: hippocampus, cerebellum, cortex and substantia nigra.
Species:  Mouse
Technique:  In situ hybridisation
References:  28
Hippocampus CA1/3 cells, dentate gyrus cells.
Species:  Rat
Technique:  Immunohistochemistry
References:  3,6
Physiological Functions
Regulation of growth cone extension.
Species:  Rat
Tissue:  Brain
References:  5,7
Possible component of muscarininc activated current in gastric smooth muscle cells.
Species:  Mouse
Tissue:  Gastric smooth muscle.
References:  16
Contributes to cold sensation in peripheral neurons.
Species:  Mouse
Tissue:  Dorsal root ganglion neurons
References:  37
Contributes to receptor activated current in amygdala neurons to influence fear and anxiety behavior.
Species:  Mouse
Tissue:  Brain: amygdala
References:  28
Contributes to calcium entry that causes growth cone collapse in hippocampal neurons.
Species:  Mouse
Tissue:  Brain: hippocampal neurons
References:  13
Controls dendrite patterning in cerebellar granule neurons.
Species:  Mouse
Tissue:  Brain: cerebellum
References:  27
Phenotypes, Alleles and Disease Models Mouse data from MGI

Show »

Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Trpc5tm1.1Clph Trpc5tm1.1Clph/Trpc5tm1.1Clph
involves: 129/Sv
MGI:109524  MP:0002910 abnormal excitatory postsynaptic currents PMID: 19450521 
Trpc5tm1.1Clph Trpc5tm1.1Clph/Y
involves: 129/Sv
MGI:109524  MP:0002910 abnormal excitatory postsynaptic currents PMID: 19450521 
Trpc5tm1.1Clph Trpc5tm1.1Clph/Trpc5tm1.1Clph
involves: 129/Sv
MGI:109524  MP:0001364 decreased anxiety-related response PMID: 19450521 
Trpc5tm1.1Clph Trpc5tm1.1Clph/Y
involves: 129/Sv
MGI:109524  MP:0001364 decreased anxiety-related response PMID: 19450521 
Trpc5tm1.1Clph Trpc5tm1.1Clph/Trpc5tm1.1Clph
involves: 129/Sv
MGI:109524  MP:0003460 decreased fear-related response PMID: 19450521 
Trpc5tm1.1Clph Trpc5tm1.1Clph/Y
involves: 129/Sv
MGI:109524  MP:0003460 decreased fear-related response PMID: 19450521 
Trpc5tm1.1Clph Trpc5tm1.1Clph/Trpc5tm1.1Clph
involves: 129/Sv
MGI:109524  MP:0003459 increased fear-related response PMID: 19450521 
Trpc5tm1.1Clph Trpc5tm1.1Clph/Y
involves: 129/Sv
MGI:109524  MP:0003459 increased fear-related response PMID: 19450521 

REFERENCES

1. Blair NT, Kaczmarek JS, Clapham DE. (2009) Intracellular calcium strongly potentiates agonist-activated TRPC5 channels. J. Gen. Physiol.133 (5): 525-46. [PMID:19398778]

2. Chakraborty S, Berwick ZC, Bartlett PJ, Kumar S, Thomas AP, Sturek M, Tune JD, Obukhov AG. (2011) Bromoenol lactone inhibits voltage-gated Ca2+ and transient receptor potential canonical channels. J. Pharmacol. Exp. Ther.339 (2): 329-40. [PMID:21795434]

3. Chung YH, Sun Ahn H, Kim D, Hoon Shin D, Su Kim S, Yong Kim K, Bok Lee W, Ik Cha C. (2006) Immunohistochemical study on the distribution of TRPC channels in the rat hippocampus. Brain Res.1085 (1): 132-7. [PMID:16580647]

4. Dattilo M, Penington NJ, Williams K. (2008) Inhibition of TRPC5 channels by intracellular ATP. Mol. Pharmacol.73 (1): 42-9. [PMID:17925457]

5. Davare MA, Fortin DA, Saneyoshi T, Nygaard S, Kaech S, Banker G, Soderling TR, Wayman GA. (2009) Transient receptor potential canonical 5 channels activate Ca2+/calmodulin kinase Igamma to promote axon formation in hippocampal neurons. J. Neurosci.29 (31): 9794-808. [PMID:19657032]

6. De March Z, Giampa  C, Patassini S, Bernardi G, Fusco FR. (2006) Cellular localization of TRPC5 in the substantia nigra of rat. Neurosci. Lett.402 (1-2): 35-9. [PMID:16635549]

7. Greka A, Navarro B, Oancea E, Duggan A, Clapham DE. (2003) TRPC5 is a regulator of hippocampal neurite length and growth cone morphology. Nat. Neurosci.6 (8): 837-45. [PMID:12858178]

8. Gross SA, Guzmán GA, Wissenbach U, Philipp SE, Zhu MX, Bruns D, Cavalié A. (2009) TRPC5 is a Ca2+-activated channel functionally coupled to Ca2+-selective ion channels. J. Biol. Chem.284 (49): 34423-32. [PMID:19815560]

9. 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. Acta1778 (4): 974-82. [PMID:18261457]

10. Hui H, McHugh D, Hannan M, Zeng F, Xu SZ, Khan SU, Levenson R, Beech DJ, Weiss JL. (2006) Calcium-sensing mechanism in TRPC5 channels contributing to retardation of neurite outgrowth. J. Physiol. (Lond.)572 (Pt 1): 165-72. [PMID:16469785]

11. Jeon JP, Hong C, Park EJ, Jeon JH, Cho NH, Kim IG, Choe H, Muallem S, Kim HJ, So I. (2012) Selective Gαi subunits as novel direct activators of transient receptor potential canonical (TRPC)4 and TRPC5 channels. J. Biol. Chem.287 (21): 17029-39. [PMID:22457348]

12. Jung S, Muhle A, Schaefer M, Strotmann R, Schultz G, Plant TD. (2003) Lanthanides potentiate TRPC5 currents by an action at extracellular sites close to the pore mouth. J. Biol. Chem.278 (6): 3562-71. [PMID:12456670]

13. Kaczmarek JS, Riccio A, Clapham DE. (2012) Calpain cleaves and activates the TRPC5 channel to participate in semaphorin 3A-induced neuronal growth cone collapse. Proc. Natl. Acad. Sci. U.S.A.109 (20): 7888-92. [PMID:22547824]

14. Kinoshita-Kawada M, Tang J, Xiao R, Kaneko S, Foskett JK, Zhu MX. (2005) Inhibition of TRPC5 channels by Ca2+-binding protein 1 in Xenopus oocytes. Pflugers Arch.450 (5): 345-54. [PMID:15895247]

15. Kraft R. (2007) The Na+/Ca2+ exchange inhibitor KB-R7943 potently blocks TRPC channels. Biochem. Biophys. Res. Commun.361 (1): 230-6. [PMID:17658472]

16. Lee YM, Kim BJ, Kim HJ, Yang DK, Zhu MH, Lee KP, So I, Kim KW. (2003) TRPC5 as a candidate for the nonselective cation channel activated by muscarinic stimulation in murine stomach. Am. J. Physiol. Gastrointest. Liver Physiol.284 (4): G604-16. [PMID:12631560]

17. 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]

18. Majeed Y, Amer MS, Agarwal AK, McKeown L, Porter KE, O'Regan DJ, Naylor J, Fishwick CW, Muraki K, Beech DJ. (2011) Stereo-selective inhibition of transient receptor potential TRPC5 cation channels by neuroactive steroids. Br. J. Pharmacol.162 (7): 1509-20. [PMID:21108630]

19. 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]

20. Miehe S, Bieberstein A, Arnould I, Ihdene O, Rütten H, Strübing C. (2010) The phospholipid-binding protein SESTD1 is a novel regulator of the transient receptor potential channels TRPC4 and TRPC5. J. Biol. Chem.285 (16): 12426-34. [PMID:20164195]

21. Miller M, Shi J, Zhu Y, Kustov M, Tian JB, Stevens A, Wu M, Xu J, Long S, Yang P et al.. (2011) Identification of ML204, a novel potent antagonist that selectively modulates native TRPC4/C5 ion channels. J. Biol. Chem.286 (38): 33436-46. [PMID:21795696]

22. Obukhov AG, Nowycky MC. (2005) A cytosolic residue mediates Mg2+ block and regulates inward current amplitude of a transient receptor potential channel. J. Neurosci.25 (5): 1234-9. [PMID:15689561]

23. Obukhov AG, Nowycky MC. (2008) TRPC5 channels undergo changes in gating properties during the activation-deactivation cycle. J. Cell. Physiol.216 (1): 162-71. [PMID:18247362]

24. Okada T, Shimizu S, Wakamori M, Maeda A, Kurosaki T, Takada N, Imoto K, Mori Y. (1998) Molecular cloning and functional characterization of a novel receptor-activated TRP Ca2+ channel from mouse brain. J. Biol. Chem.273 (17): 10279-87. [PMID:9553080]

25. Ordaz B, Tang J, Xiao R, Salgado A, Sampieri A, Zhu MX, Vaca L. (2005) Calmodulin and calcium interplay in the modulation of TRPC5 channel activity. Identification of a novel C-terminal domain for calcium/calmodulin-mediated facilitation. J. Biol. Chem.280 (35): 30788-96. [PMID:15987684]

26. Philipp S, Hambrecht J, Braslavski L, Schroth G, Freichel M, Murakami M, Cavalié A, Flockerzi V. (1998) A novel capacitative calcium entry channel expressed in excitable cells. EMBO J.17 (15): 4274-82. [PMID:9687496]

27. Puram SV, Riccio A, Koirala S, Ikeuchi Y, Kim AH, Corfas G, Bonni A. (2011) A TRPC5-regulated calcium signaling pathway controls dendrite patterning in the mammalian brain. Genes Dev.25 (24): 2659-73. [PMID:22135323]

28. Riccio A, Li Y, Moon J, Kim KS, Smith KS, Rudolph U, Gapon S, Yao GL, Tsvetkov E, Rodig SJ et al.. (2009) Essential role for TRPC5 in amygdala function and fear-related behavior. Cell137 (4): 761-72. [PMID:19450521]

29. Schaefer M, Plant TD, Obukhov AG, Hofmann T, Gudermann T, Schultz G. (2000) Receptor-mediated regulation of the nonselective cation channels TRPC4 and TRPC5. J. Biol. Chem.275 (23): 17517-26. [PMID:10837492]

30. Strübing C, Krapivinsky G, Krapivinsky L, Clapham DE. (2001) TRPC1 and TRPC5 form a novel cation channel in mammalian brain. Neuron29 (3): 645-55. [PMID:11301024]

31. 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]

32. Tang Y, Tang J, Chen Z, Trost C, Flockerzi V, Li M, Ramesh V, Zhu MX. (2000) Association of mammalian trp4 and phospholipase C isozymes with a PDZ domain-containing protein, NHERF. J. Biol. Chem.275 (48): 37559-64. [PMID:10980202]

33. Wong CO, Huang Y, Yao X. (2010) Genistein potentiates activity of the cation channel TRPC5 independently of tyrosine kinases. Br. J. Pharmacol.159 (7): 1486-96. [PMID:20233211]

34. 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]

35. Yoshida T, Inoue R, Morii T, Takahashi N, Yamamoto S, Hara Y, Tominaga M, Shimizu S, Sato Y, Mori Y. (2006) Nitric oxide activates TRP channels by cysteine S-nitrosylation. Nat. Chem. Biol.2 (11): 596-607. [PMID:16998480]

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. Zimmermann K, Lennerz JK, Hein A, Link AS, Kaczmarek JS, Delling M, Uysal S, Pfeifer JD, Riccio A, Clapham DE. (2011) Transient receptor potential cation channel, subfamily C, member 5 (TRPC5) is a cold-transducer in the peripheral nervous system. Proc. Natl. Acad. Sci. U.S.A.108 (44): 18114-9. [PMID:22025699]

To cite this database page, please use the following:

Nathaniel T Blair, David E. Clapham.
Transient Receptor Potential channels: TRPC5. Last modified on 13/02/2014. Accessed on 02/10/2014. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=490.

Contact us | Print | Back to top | Help
Copyright © 2014 IUPHAR