TRPC3

Protein and coding gene in humans

TRPC3

Identifiers

Aliases

TRPC3, SCA41, TRP3, transient receptor potential cation channel subfamily C member 3

External IDs

OMIM: 602345; MGI: 109526; HomoloGene: 20708; GeneCards: TRPC3; OMA:TRPC3 - orthologs

Gene location (Human)

Chr.	Chromosome 4 (human)^[1]

Band	4q27	Start	121,874,481 bp^[1]
Band	4q27	End	121,952,060 bp^[1]

Gene location (Mouse)

Chr.	Chromosome 3 (mouse)^[2]

Band	3 B\|3 17.93 cM	Start	36,674,631 bp^[2]
Band	3 B\|3 17.93 cM	End	36,744,316 bp^[2]

RNA expression pattern

Bgee

Human

Mouse (ortholog)

Top expressed in

secondary oocyte

endothelial cell

pituitary gland

anterior pituitary

gastric mucosa

putamen

ganglionic eminence

prefrontal cortex

stromal cell of endometrium

caudate nucleus

Top expressed in

cerebellar vermis

medial dorsal nucleus

lateral geniculate nucleus

medial geniculate nucleus

medial vestibular nucleus

superior colliculus

superior frontal gyrus

globus pallidus

pineal gland

dorsal tegmental nucleus

More reference expression data

BioGPS


More reference expression data

Gene ontology
Molecular function	store-operated calcium channel activity calcium channel activity inositol 1,4,5 trisphosphate binding ion channel activity protein binding
Cellular component	integral component of membrane membrane plasma membrane integral component of plasma membrane cation channel complex
Biological process	response to ATP positive regulation of calcium ion transport into cytosol ion transport single fertilization platelet activation response to calcium ion calcium ion transmembrane transport positive regulation of cardiac muscle hypertrophy in response to stress manganese ion transport calcium ion transport phototransduction transmembrane transport regulation of cytosolic calcium ion concentration
Sources:Amigo / QuickGO

Orthologs

Species

Human

Mouse

Entrez


7222


22065

Ensembl


ENSG00000138741


ENSMUSG00000027716

UniProt


Q13507


Q9QZC1

RefSeq (mRNA)


NM_001130698 NM_003305 NM_001366479


NM_019510

RefSeq (protein)


NP_001124170 NP_003296 NP_001353408


n/a

Location (UCSC)

Chr 4: 121.87 – 121.95 Mb

Chr 3: 36.67 – 36.74 Mb

PubMed search

^[3]

^[4]

Wikidata

View/Edit Human

View/Edit Mouse

Short transient receptor potential channel 3 (TrpC3) also known as transient receptor protein 3 (TRP-3) is a protein that in humans is encoded by the TRPC3 gene. The TRPC3/6/7 subfamily are implicated in the regulation of vascular tone, cell growth, proliferation and pathological hypertrophy.^[5] These are diacylglycerol-sensitive cation channels known to regulate intracellular calcium via activation of the phospholipase C (PLC) pathway and/or by sensing Ca2+ store depletion.^[6] Together, their role in calcium homeostasis has made them potential therapeutic targets for a variety of central and peripheral pathologies.^[7]

Function

Non-specific cation conductance elicited by the activation of TrkB by BDNF is TRPC3-dependent in the CNS.^[8] TRPC channels are almost always co-localized with mGluR1-expressing cells and likely play a role in mGluR-mediated EPSPs.^[9]

The TRPC3 channel has been shown to be preferentially expressed in non-excitable cell types, such as oligodendrocytes.^[6] However, evidence suggests that active TRPC3 channels in basal ganglia (BG) output neurons are responsible for maintaining a tonic inward depolarizing current that regulates resting membrane potential and promotes regular neuronal firing.^[10] Conversely, inhibiting TRPC3 promotes cellular hyperpolarization, which can lead to slower and more irregular neuronal firing. While it's unclear if TRPC3 channels have equal expression, other members of the TRPC family have been localized to the axon hillock, cell body, and dendritic processes of dopamine-expressing cells.^[11]

The neuromodulator, substance P, activates TRPC3/7 channels inducing cellular currents that underlie rhythmic pacemaker activity in the brainstem, enhancing the regularity and frequency of respiratory rhythms,^[12] showing homology to the mechanism described in BG neurons. Transgenic cardiomyocytes expressing TRPC3 show prolonged action potential duration when exposed to a TRPC3 agonist.^[13] The same cardiomyocytes also increase their firing rate with agonist exposure under a current-clamp tetanus protocol suggesting that they may play a role in cardiac arrhythmogenesis.

Modulators

A small molecule agonist is GSK1702934A and antagonists are GSK417651A and GSK2293017A.^[5] A commercially available inhibitor is available in the form of a pyrazole compound, Pyr3^[14] TRPC3 has been shown to specifically interact with TRPC1^[15]^[16] and TRPC6.^[17]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000138741 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000027716 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ ^a ^b Xu X, Lozinskaya I, Costell M, Lin Z, Ball JA, Bernard R, Behm DJ, Marino JP, Schnackenberg CG (2013-01-29). "Characterization of Small Molecule TRPC3 and TRPC6 agonist and Antagonists". Biophysical Journal. 104 (2, Supplement 1): 454a. Bibcode:2013BpJ...104..454X. doi:10.1016/j.bpj.2012.11.2513.
^ ^a ^b Fusco FR, Martorana A, Giampà C, De March Z, Vacca F, Tozzi A, Longone P, Piccirilli S, Paolucci S, Sancesario G, Mercuri NB, Bernardi G (July 2004). "Cellular localization of TRPC3 channel in rat brain: preferential distribution to oligodendrocytes". Neuroscience Letters. 365 (2): 137–42. doi:10.1016/j.neulet.2004.04.070. PMID 15245795. S2CID 27636840.
^ Kaneko Y, Szallasi A (2013-01-01). "TRP channels as therapeutic targets". Current Topics in Medicinal Chemistry. 13 (3): 241–3. doi:10.2174/1568026611313030001. PMID 23432057.
^ Li HS, Xu XZ, Montell C (1999). "Activation of a TRPC3-dependent cation current through the neurotrophin BDNF". Neuron. 24 (1): 261–73. doi:10.1016/S0896-6273(00)80838-7. PMID 10677043. S2CID 16174327.
^ Giampà C, DeMarch Z, Patassini S, Bernardi G, Fusco FR (September 2007). "Immunohistochemical localization of TRPC6 in the rat substantia nigra". Neuroscience Letters. 424 (3): 170–4. doi:10.1016/j.neulet.2007.07.049. PMID 17723267. S2CID 43481432.
^ Zhou FW, Matta SG, Zhou FM (January 2008). "Constitutively active TRPC3 channels regulate basal ganglia output neurons". The Journal of Neuroscience. 28 (2): 473–82. doi:10.1523/JNEUROSCI.3978-07.2008. PMC 3652281. PMID 18184790.
^ Zhu MX, Huang J, Du W, Yao H, Wang Y (2011). "TRPC Channels in Neuronal Survival". In Zhu MX (ed.). TRPC Channels in Neuronal Surviva. Boca Raton (FL): CRC Press/Taylor & Francis. ISBN 978-1-4398-1860-2. PMID 22593969.
^ Ben-Mabrouk F, Tryba AK (April 2010). "Substance P modulation of TRPC3/7 channels improves respiratory rhythm regularity and ICAN-dependent pacemaker activity". The European Journal of Neuroscience. 31 (7): 1219–32. doi:10.1111/j.1460-9568.2010.07156.x. PMC 3036165. PMID 20345918.
^ Doleschal B, Primessnig U, Wölkart G, Wolf S, Schernthaner M, Lichtenegger M, Glasnov TN, Kappe CO, Mayer B, Antoons G, Heinzel F, Poteser M, Groschner K (April 2015). "TRPC3 contributes to regulation of cardiac contractility and arrhythmogenesis by dynamic interaction with NCX1". Cardiovascular Research. 106 (1): 163–73. doi:10.1093/cvr/cvv022. PMC 4362401. PMID 25631581.
^ Kiyonaka S, Kato K, Nishida M, Mio K, Numaga T, Sawaguchi Y, Yoshida T, Wakamori M, Mori E, Numata T, Ishii M, Takemoto H, Ojida A, Watanabe K, Uemura A, Kurose H, Morii T, Kobayashi T, Sato Y, Sato C, Hamachi I, Mori Y (March 2009). "Selective and direct inhibition of TRPC3 channels underlies biological activities of a pyrazole compound". Proceedings of the National Academy of Sciences of the United States of America. 106 (13): 5400–5. Bibcode:2009PNAS..106.5400K. doi:10.1073/pnas.0808793106. PMC 2664023. PMID 19289841.
^ Strübing C, Krapivinsky G, Krapivinsky L, Clapham DE (October 2003). "Formation of novel TRPC channels by complex subunit interactions in embryonic brain". The Journal of Biological Chemistry. 278 (40): 39014–9. doi:10.1074/jbc.M306705200. PMID 12857742.
^ Xu XZ, Li HS, Guggino WB, Montell C (June 1997). "Coassembly of TRP and TRPL produces a distinct store-operated conductance". Cell. 89 (7): 1155–64. doi:10.1016/S0092-8674(00)80302-5. PMID 9215637. S2CID 15275438.
^ Hofmann T, Schaefer M, Schultz G, Gudermann T (May 2002). "Subunit composition of mammalian transient receptor potential channels in living cells". Proceedings of the National Academy of Sciences of the United States of America. 99 (11): 7461–6. Bibcode:2002PNAS...99.7461H. doi:10.1073/pnas.102596199. PMC 124253. PMID 12032305.

External links

TRPC3+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

Membrane transport protein: ion channels (TC 1A)

Ca²⁺: Calcium channel

Ligand-gated	Inositol trisphosphate receptor 1 2 3 Ryanodine receptor 1 2 3
Voltage-gated	L-type/Ca_vα 1.1 1.2 1.3 1.4 N-type/Ca_vα2.2 P-type/Ca_vα 2.1 Q-type/Ca_vα2.1 R-type/Ca_vα2.3 T-type/Ca_vα 3.1 3.2 3.3 α₂δ-subunits 1 2 β-subunits β1 β2 β3 β4 γ-subunits γ1 γ2 γ3 γ4 Cation channels of sperm 1 2 3 4 Two-pore channel 1 2

Na⁺: Sodium channel

Constitutively active	Epithelial sodium channel α β γ δ
Proton-gated	Amiloride-sensitive cation channel 1 2 3 4
Voltage-gated	Na_vα 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 1.9 7A Na_vβ 1 2 3 4

K⁺: Potassium channel

Calcium-activated	BK channel α1 β1 β2 β3 β4 SK channel SK1 SK2 SK3 IK channel IK1 K_Ca 1.1 2.1 2.2 2.3 3.1 4.1 4.2 5.1
Inward-rectifier	K_ATP K_ir 1.1 2.1 2.2 2.3 2.4 2.6 GIRK/K_ir 3.1 3.2 3.3 3.4 K_ir 4.1 4.2 5.1 6.1 6.2 7.1
Tandem pore domain	K2P 1 2 3 4 5 6 7 9 10 12 13 15 16 17 18
Voltage-gated	K_vα1-6 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 2.1 2.2 3.1 3.2 3.3 3.4 4.1 4.2 4.3 5.1 6.1 6.2 6.3 6.4 K_vα7-12 7.1 7.2 7.3 7.4 7.5 8.1 8.2 9.1 9.2 9.3 10.1 10.2 11.1/hERG 11.2 11.3 12.1 12.2 12.3 K_vβ 1 2 3 KCNIP 1 2 3 4 minK/ISK minK/ISK-like MiRP 1 2 3 Shaker (gene)

Miscellaneous

Cl⁻: Chloride channel	Calcium-activated chloride channels Anoctamin ANO1 Bestrophin 1 2 Chloride Channel Accessory 1 2 3 4 CFTR CLCN 1 2 3 4 5 6 7 KA KB CLIC 1 2 3 4 5 6 L1 CLNS 1A 1B
H⁺: Proton channel	HVCN1
M⁺: CNG cation channel	α 1 2 3 4 β 1 2 3 HCN FC 1 2 3 4
M⁺: TRP cation channel	TRPA (1) TRPC 1 2 3 4 4AP 5 6 7 TRPM 1 2 3 4 5 6 7 8 TRPML 1 2 3 TRPN TRPP 1 2 TRPV 1 2 3 4 5 6
H₂O (+ solutes): Porin	Aquaporin 0 1 2 3 4 5 6 7 8 9 Voltage-dependent anion channel 1 2 3 General bacterial porin family
Cytoplasm: Gap junction	Connexin A GJA1 GJA3 GJA4 GJA5 GJA8 GJA9 GJA10 B GJB1 GJB2 GJB3 GJB4 GJB5 GJB6 GJB7 C GJC1 GJC2 GJC3 D GJD2 GJD3 GJD4 Innexin

By gating mechanism

Ion channel class	Ligand-gated Light-gated Voltage-gated Stretch-activated

see also disorders

TRP channel modulators

TRPA

Activators

4-Hydroxynonenal
4-Oxo-2-nonenal
4,5-EET
12S-HpETE
15-Deoxy-Δ^12,14-prostaglandin J2
α-Sanshool (ginger, Sichuan and melegueta peppers)
Acrolein
Allicin (garlic)
Allyl isothiocyanate (mustard, radish, horseradish, wasabi)
AM404
ASP-7663
Bradykinin
Cannabichromene (cannabis)
Cannabidiol (cannabis)
Cannabigerol (cannabis)
Cinnamaldehyde (cinnamon)
CR gas (dibenzoxazepine; DBO)
CS gas (2-chlorobenzal malononitrile)
Cuminaldehyde (cumin)
Curcumin (turmeric)
Dehydroligustilide (celery)
Diallyl disulfide
Dicentrine (Lindera spp.)
Farnesyl thiosalicylic acid
Formalin
Gingerols (ginger)
Hepoxilin A3
Hepoxilin B3
Hydrogen peroxide
Icilin
Isothiocyanate
JT-010
Ligustilide (celery, Angelica acutiloba)
Linalool (Sichuan pepper, thyme)
Methylglyoxal
Methyl salicylate (wintergreen)
N-Methylmaleimide
Nicotine (tobacco)
Oleocanthal (olive oil)
Paclitaxel (Pacific yew)
Paracetamol (acetaminophen)
PF-4840154
Phenacyl chloride
Polygodial (Dorrigo pepper)
Shogaols (ginger, Sichuan and melegueta peppers)
Tear gases
Tetrahydrocannabinol (cannabis)
Tetrahydrocannabiorcol
Thiopropanal S-oxide (onion)
Umbellulone (Umbellularia californica)
WIN 55,212-2

Blockers

TRPC

Activators	Adhyperforin (St John's wort) Diacyl glycerol GSK1702934A Hyperforin (St John's wort) Substance P
Blockers	DCDPC DHEA-S Flufenamic acid GSK417651A GSK2293017A Meclofenamic acid N-(p-Amylcinnamoyl)anthranilic acid Niflumic acid Pregnenolone sulfate Progesterone Pyr3 Tolfenamic acid