TRPC3

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.{{Cite journal | vauthors = Xu X, Lozinskaya I, Costell M, Lin Z, Ball JA, Bernard R, Behm DJ, Marino JP, Schnackenberg CG | title = Characterization of Small Molecule TRPC3 and TRPC6 agonist and Antagonists | journal = Biophysical Journal | volume = 104 | issue = 2, Supplement 1 | pages = 454a | date = 2013-01-29 | doi = 10.1016/j.bpj.2012.11.2513 | bibcode = 2013BpJ...104..454X | doi-access = free }} 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.{{cite journal | vauthors = 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 | title = Cellular localization of TRPC3 channel in rat brain: preferential distribution to oligodendrocytes | journal = Neuroscience Letters | volume = 365 | issue = 2 | pages = 137–142 | date = July 2004 | pmid = 15245795 | doi = 10.1016/j.neulet.2004.04.070 | s2cid = 27636840 }} Together, their role in calcium homeostasis has made them potential therapeutic targets for a variety of central and peripheral pathologies.{{cite journal | vauthors = Kaneko Y, Szallasi A | title = TRP channels as therapeutic targets | journal = Current Topics in Medicinal Chemistry | volume = 13 | issue = 3 | pages = 241–243 | date = 2013-01-01 | pmid = 23432057 | doi = 10.2174/1568026611313030001 }}

Function

Non-specific cation conductance elicited by the activation of TrkB by BDNF is TRPC3-dependent in the CNS.{{cite journal | vauthors = Li HS, Xu XZ, Montell C | title = Activation of a TRPC3-dependent cation current through the neurotrophin BDNF | journal = Neuron | volume = 24 | issue = 1 | pages = 261–273 | year = 1999 | pmid = 10677043 | doi = 10.1016/S0896-6273(00)80838-7 | s2cid = 16174327 | doi-access = free }} TRPC channels are almost always co-localized with mGluR1-expressing cells and likely play a role in mGluR-mediated EPSPs.{{cite journal | vauthors = Giampà C, DeMarch Z, Patassini S, Bernardi G, Fusco FR | title = Immunohistochemical localization of TRPC6 in the rat substantia nigra | journal = Neuroscience Letters | volume = 424 | issue = 3 | pages = 170–174 | date = September 2007 | pmid = 17723267 | doi = 10.1016/j.neulet.2007.07.049 | s2cid = 43481432 }}

The TRPC3 channel has been shown to be preferentially expressed in non-excitable cell types, such as oligodendrocytes. 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.{{cite journal | vauthors = Zhou FW, Matta SG, Zhou FM | title = Constitutively active TRPC3 channels regulate basal ganglia output neurons | journal = The Journal of Neuroscience : The Official Journal of the Society for Neuroscience | volume = 28 | issue = 2 | pages = 473–482 | date = January 2008 | pmid = 18184790 | pmc = 3652281 | doi = 10.1523/JNEUROSCI.3978-07.2008 }} 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.{{cite book | vauthors = Zhu MX, Huang J, Du W, Yao H, Wang Y | veditors = Zhu MX | chapter = TRPC Channels in Neuronal Survival | title = TRPC Channels in Neuronal Surviva | location = Boca Raton (FL) | year = 2011 | pmid = 22593969 | isbn = 978-1-4398-1860-2 | publisher = CRC Press/Taylor & Francis | url = https://www.ncbi.nlm.nih.gov/books/NBK92826/ }}

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,{{cite journal | vauthors = Ben-Mabrouk F, Tryba AK | title = Substance P modulation of TRPC3/7 channels improves respiratory rhythm regularity and ICAN-dependent pacemaker activity | journal = The European Journal of Neuroscience | volume = 31 | issue = 7 | pages = 1219–1232 | date = April 2010 | pmid = 20345918 | pmc = 3036165 | doi = 10.1111/j.1460-9568.2010.07156.x }} showing homology to the mechanism described in BG neurons. Transgenic cardiomyocytes expressing TRPC3 show prolonged action potential duration when exposed to a TRPC3 agonist.{{cite journal | vauthors = 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 | title = TRPC3 contributes to regulation of cardiac contractility and arrhythmogenesis by dynamic interaction with NCX1 | journal = Cardiovascular Research | volume = 106 | issue = 1 | pages = 163–173 | date = April 2015 | pmid = 25631581 | pmc = 4362401 | doi = 10.1093/cvr/cvv022 }} 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. A commercially available inhibitor is available in the form of a pyrazole compound, Pyr3{{cite journal | vauthors = 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 | title = Selective and direct inhibition of TRPC3 channels underlies biological activities of a pyrazole compound | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 106 | issue = 13 | pages = 5400–5405 | date = March 2009 | pmid = 19289841 | pmc = 2664023 | doi = 10.1073/pnas.0808793106 | bibcode = 2009PNAS..106.5400K | doi-access = free }} TRPC3 has been shown to specifically interact with TRPC1{{cite journal | vauthors = Strübing C, Krapivinsky G, Krapivinsky L, Clapham DE | title = Formation of novel TRPC channels by complex subunit interactions in embryonic brain | journal = The Journal of Biological Chemistry | volume = 278 | issue = 40 | pages = 39014–39019 | date = October 2003 | pmid = 12857742 | doi = 10.1074/jbc.M306705200 | doi-access = free }}{{cite journal | vauthors = Xu XZ, Li HS, Guggino WB, Montell C | title = Coassembly of TRP and TRPL produces a distinct store-operated conductance | journal = Cell | volume = 89 | issue = 7 | pages = 1155–1164 | date = June 1997 | pmid = 9215637 | doi = 10.1016/S0092-8674(00)80302-5 | s2cid = 15275438 | doi-access = free }} and TRPC6.{{cite journal | vauthors = Hofmann T, Schaefer M, Schultz G, Gudermann T | title = Subunit composition of mammalian transient receptor potential channels in living cells | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 99 | issue = 11 | pages = 7461–7466 | date = May 2002 | pmid = 12032305 | pmc = 124253 | doi = 10.1073/pnas.102596199 | bibcode = 2002PNAS...99.7461H | doi-access = free }}

References

External links

{{MeshName|TRPC3+protein,+human}}

Category:Ion channels

TRPC3

Function

Modulators

See also

References

Further reading

External links