TRPC3

Last updated
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
Orthologs
SpeciesHumanMouse
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]

Contents

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]

See also

Related Research Articles

Transient receptor potential channels are a group of ion channels located mostly on the plasma membrane of numerous animal cell types. Most of these are grouped into two broad groups: Group 1 includes TRPC, TRPV, TRPVL, TRPM, TRPS, TRPN, and TRPA. Group 2 consists of TRPP and TRPML. Other less-well categorized TRP channels exist, including yeast channels and a number of Group 1 and Group 2 channels present in non-animals. Many of these channels mediate a variety of sensations such as pain, temperature, different kinds of tastes, pressure, and vision. In the body, some TRP channels are thought to behave like microscopic thermometers and used in animals to sense hot or cold. Some TRP channels are activated by molecules found in spices like garlic (allicin), chili pepper (capsaicin), wasabi ; others are activated by menthol, camphor, peppermint, and cooling agents; yet others are activated by molecules found in cannabis or stevia. Some act as sensors of osmotic pressure, volume, stretch, and vibration. Most of the channels are activated or inhibited by signaling lipids and contribute to a family of lipid-gated ion channels.

<span class="mw-page-title-main">Neuronal calcium sensor-1</span> Protein-coding gene in the species Homo sapiens

Neuronal calcium sensor-1 (NCS-1) also known as frequenin homolog (Drosophila) (freq) is a protein that is encoded by the FREQ gene in humans. NCS-1 is a member of the neuronal calcium sensor family, a class of EF hand containing calcium-myristoyl-switch proteins.

<span class="mw-page-title-main">TRPV1</span> Human protein for regulating body temperature

The transient receptor potential cation channel subfamily V member 1 (TrpV1), also known as the capsaicin receptor and the vanilloid receptor 1, is a protein that, in humans, is encoded by the TRPV1 gene. It was the first isolated member of the transient receptor potential vanilloid receptor proteins that in turn are a sub-family of the transient receptor potential protein group. This protein is a member of the TRPV group of transient receptor potential family of ion channels.

TRPC is a family of transient receptor potential cation channels in animals.

<span class="mw-page-title-main">TRPV</span> Subgroup of TRP cation channels named after the vanilloid receptor

TRPV is a family of transient receptor potential cation channels in animals. All TRPVs are highly calcium selective.

<span class="mw-page-title-main">MCOLN1</span> Protein-coding gene in the species Homo sapiens

Mucolipin-1 also known as TRPML1 is a protein that in humans is encoded by the MCOLN1 gene. It is a member of the small family of the TRPML channels, a subgroup of the large protein family of TRP ion channels.

<span class="mw-page-title-main">TRPC6</span> Protein and coding gene in humans

Transient receptor potential cation channel, subfamily C, member 6, also known as TRPC6, is a human gene encoding a protein of the same name. TRPC6 is a transient receptor potential channel of the classical TRPC subfamily. It has been associated with depression and anxiety, as well as with focal segmental glomerulosclerosis (FSGS).

<span class="mw-page-title-main">TRPC1</span> Protein and coding gene in humans

Transient receptor potential canonical 1 (TRPC1) is a protein that in humans is encoded by the TRPC1 gene.

<span class="mw-page-title-main">TRPC4</span> Protein and coding gene in humans

The short transient receptor potential channel 4 (TrpC4), also known as Trp-related protein 4, is a protein that in humans is encoded by the TRPC4 gene.

<span class="mw-page-title-main">TRPC5</span> Protein-coding gene in the species Homo sapiens

Short transient receptor potential channel 5 (TrpC5) also known as transient receptor protein 5 (TRP-5) is a protein that in humans is encoded by the TRPC5 gene. TrpC5 is subtype of the TRPC family of mammalian transient receptor potential ion channels.

<span class="mw-page-title-main">TRPM5</span> Protein-coding gene in the species Homo sapiens

Transient receptor potential cation channel subfamily M member 5 (TRPM5), also known as long transient receptor potential channel 5 is a protein that in humans is encoded by the TRPM5 gene.

<span class="mw-page-title-main">TRPV2</span> Protein-coding gene in the species Homo sapiens

Transient receptor potential cation channel subfamily V member 2 is a protein that in humans is encoded by the TRPV2 gene. TRPV2 is a nonspecific cation channel that is a part of the TRP channel family. This channel allows the cell to communicate with its extracellular environment through the transfer of ions, and responds to noxious temperatures greater than 52 °C. It has a structure similar to that of potassium channels, and has similar functions throughout multiple species; recent research has also shown multiple interactions in the human body.

<span class="mw-page-title-main">TRPV4</span> Protein-coding gene in the species Homo sapiens

Transient receptor potential cation channel subfamily V member 4 is an ion channel protein that in humans is encoded by the TRPV4 gene.

<span class="mw-page-title-main">TRPM8</span> Protein-coding gene in the species Homo sapiens

Transient receptor potential cation channel subfamily M (melastatin) member 8 (TRPM8), also known as the cold and menthol receptor 1 (CMR1), is a protein that in humans is encoded by the TRPM8 gene. The TRPM8 channel is the primary molecular transducer of cold somatosensation in humans. In addition, mints can desensitize a region through the activation of TRPM8 receptors.

<span class="mw-page-title-main">TRPM3</span> Protein-coding gene in the species Homo sapiens

Transient receptor potential cation channel subfamily M member 3 is a protein that in humans is encoded by the TRPM3 gene.

<span class="mw-page-title-main">TRPV3</span> Protein-coding gene in the species Homo sapiens

Transient receptor potential cation channel, subfamily V, member 3, also known as TRPV3, is a human gene encoding the protein of the same name.

<span class="mw-page-title-main">Polycystin 2</span> Protein and coding gene in humans

Polycystin-2 is a protein that in humans is encoded by the PKD2 gene.

<span class="mw-page-title-main">Calcium-binding protein 1</span> Protein-coding gene in the species Homo sapiens

Calcium binding protein 1 is a protein that in humans is encoded by the CABP1 gene. Calcium-binding protein 1 is a calcium-binding protein discovered in 1999. It has two EF hand motifs and is expressed in neuronal cells in such areas as hippocampus, habenular nucleus of the epithalamus, Purkinje cell layer of the cerebellum, and the amacrine cells and cone bipolar cells of the retina.

<span class="mw-page-title-main">MCOLN3</span> Protein-coding gene in the species Homo sapiens

Mucolipin-3 also known as TRPML3 is a protein that in humans is encoded by the MCOLN3 gene. It is a member of the small family of the TRPML channels, a subgroup of the large protein family of TRP ion channels.

The transient receptor potential Ca2+ channel (TRP-CC) family (TC# 1.A.4) is a member of the voltage-gated ion channel (VIC) superfamily and consists of cation channels conserved from worms to humans. The TRP-CC family also consists of seven subfamilies (TRPC, TRPV, TRPM, TRPN, TRPA, TRPP, and TRPML) based on their amino acid sequence homology:

  1. the canonical or classic TRPs,
  2. the vanilloid receptor TRPs,
  3. the melastatin or long TRPs,
  4. ankyrin (whose only member is the transmembrane protein 1 [TRPA1])
  5. TRPN after the nonmechanoreceptor potential C (nonpC), and the more distant cousins,
  6. the polycystins
  7. and mucolipins.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000138741 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000027716 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 1 2 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 .
  6. 1 2 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.
  7. ↑ 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.
  8. ↑ 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.
  9. ↑ 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.
  10. ↑ 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.
  11. ↑ 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.
  12. ↑ 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.
  13. ↑ 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.
  14. ↑ 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.
  15. ↑ 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.
  16. ↑ 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.
  17. ↑ 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.

Further reading

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