View source for TRPC3

{{Short description|Protein and coding gene in humans}}
{{Infobox_gene}}
'''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.<ref name="Xu_2013">{{Cite journal|last1=Xu|first1=Xiaoping|last2=Lozinskaya|first2=Irina|last3=Costell|first3=Melissa|last4=Lin|first4=Zuojun|last5=Ball|first5=Jennifer A.|last6=Bernard|first6=Roberta|last7=Behm|first7=David J.|last8=Marino|first8=Joseph P.|last9=Schnackenberg|first9=Christine G. | name-list-style = vanc |date=2013-01-29|title=Characterization of Small Molecule TRPC3 and TRPC6 agonist and Antagonists|journal=Biophysical Journal|volume=104|issue=2, Supplement 1|pages=454a|doi=10.1016/j.bpj.2012.11.2513|bibcode=2013BpJ...104..454X|doi-access=free}}</ref> These are diacylglycerol-sensitive [[Ion channel|cation channels]] known to regulate intracellular calcium via activation of the [[Phospholipase C|phospholipase C (PLC)]] pathway and/or by sensing Ca2+ store depletion.<ref name="Fusco FR 2004">{{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 = 137–42 | date = July 2004 | pmid = 15245795 | doi = 10.1016/j.neulet.2004.04.070 | s2cid = 27636840 }}</ref> Together, their role in calcium homeostasis has made them potential therapeutic targets for a variety of central and peripheral pathologies.<ref>{{cite journal | vauthors = Kaneko Y, Szallasi A | title = TRP channels as therapeutic targets | journal = Current Topics in Medicinal Chemistry | volume = 13 | issue = 3 | pages = 241–3 | date = 2013-01-01 | pmid = 23432057 | doi=10.2174/1568026611313030001}}</ref>
== Function ==
Non-specific cation conductance elicited by the activation of [[tropomyosin receptor kinase B|TrkB]] by [[brain-derived neurotrophic factor|BDNF]] is TRPC3-dependent in the CNS.<ref name="pmid10677043">{{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 = 261–73 | year = 1999 | pmid = 10677043 | doi = 10.1016/S0896-6273(00)80838-7 | s2cid = 16174327 | doi-access = free }}</ref> TRPC channels are almost always co-localized with [[Metabotropic glutamate receptor 1|mGluR1]]-expressing cells and likely play a role in mGluR-mediated [[Excitatory postsynaptic potential|EPSPs]].<ref>{{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 = 170–4 | date = September 2007 | pmid = 17723267 | doi = 10.1016/j.neulet.2007.07.049 | s2cid = 43481432 }}</ref>
The TRPC3 channel has been shown to be preferentially expressed in non-excitable cell types, such as [[oligodendrocyte]]s.<ref name="Fusco FR 2004"/> However, evidence suggests that active TRPC3 channels in [[Basal ganglia|basal ganglia (BG)]] output neurons are responsible for maintaining a tonic inward depolarizing current that regulates resting membrane potential and promotes regular neuronal firing.<ref>{{cite journal | vauthors = Zhou FW, Matta SG, Zhou FM | title = Constitutively active TRPC3 channels regulate basal ganglia output neurons | journal = The Journal of Neuroscience | volume = 28 | issue = 2 | pages = 473–82 | date = January 2008 | pmid = 18184790 | pmc = 3652281 | doi = 10.1523/JNEUROSCI.3978-07.2008 }}</ref> 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 [[Dendrite|dendritic processes]] of dopamine-expressing cells.<ref name="pmid22593969">{{cite book | vauthors = Zhu MX, Huang J, Du W, Yao H, Wang Y | title = TRPC Channels in Neuronal Surviva | chapter = TRPC Channels in Neuronal Survival | pmid = 22593969 | isbn=978-1-4398-1860-2 | editor-last = Zhu | editor-first = Michael X. |publisher=CRC Press/Taylor & Francis | location=Boca Raton (FL) | url = https://www.ncbi.nlm.nih.gov/books/NBK92826/ | year = 2011 }}</ref>
The neuromodulator, [[substance P]], activates TRPC3/7 channels inducing cellular currents that underlie rhythmic pacemaker activity in the [[Pre-Bötzinger complex|brainstem]], enhancing the regularity and frequency of respiratory rhythms,<ref>{{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 = 1219–32 | date = April 2010 | pmid = 20345918 | pmc = 3036165 | doi = 10.1111/j.1460-9568.2010.07156.x }}</ref> showing homology to the mechanism described in BG neurons. Transgenic cardiomyocytes expressing TRPC3 show prolonged action potential duration when exposed to a TRPC3 agonist.<ref>{{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 = 163–73 | date = April 2015 | pmid = 25631581 | pmc = 4362401 | doi = 10.1093/cvr/cvv022 }}</ref> 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.<ref name= "Xu_2013" /> A commercially available inhibitor is available in the form of a pyrazole compound, Pyr3<ref>{{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 = 5400–5 | date = March 2009 | pmid = 19289841 | pmc = 2664023 | doi = 10.1073/pnas.0808793106 | bibcode = 2009PNAS..106.5400K | doi-access = free }}</ref> TRPC3 has been shown to specifically [[Protein-protein interaction|interact]] with [[TRPC1]]<ref name="pmid12857742">{{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 = 39014–9 | date = October 2003 | pmid = 12857742 | doi = 10.1074/jbc.M306705200 | doi-access = free }}</ref><ref name="pmid9215637">{{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 = 1155–64 | date = June 1997 | pmid = 9215637 | doi = 10.1016/S0092-8674(00)80302-5 | s2cid = 15275438 | doi-access = free }}</ref> and [[TRPC6]].<ref name="pmid12032305">{{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 = 7461–6 | date = May 2002 | pmid = 12032305 | pmc = 124253 | doi = 10.1073/pnas.102596199 | bibcode = 2002PNAS...99.7461H | doi-access = free }}</ref>
== See also ==
* [[Transient receptor potential channel]]
* [[TRPC]]
{{clear}}
== References ==
{{Reflist|33em}}
== Further reading ==
{{refbegin|33em}}
* {{cite book | last = Islam | first = Md. Shahidul | title = Transient Receptor Potential Channels |date=January 2011 | volume = 704 | publisher = Springer |  location = Berlin | pages = 700  | series = Advances in Experimental Medicine and Biology | isbn = 978-94-007-0264-6 }}
* {{cite journal | vauthors = Lemmon MA | title = Pleckstrin homology domains: two halves make a hole? | journal = Cell | volume = 120 | issue = 5 | pages = 574–6 | date = March 2005 | pmid = 15766521 | doi = 10.1016/j.cell.2005.02.023 | s2cid = 16696677 | authorlink1 = Mark A. Lemmon | doi-access = free }}
* {{cite journal  |vauthors=Clapham DE, Julius D, Montell C, Schultz G |title=International Union of Pharmacology. XLIX. Nomenclature and structure-function relationships of transient receptor potential channels. |journal=Pharmacol. Rev. |volume=57 |issue= 4 |pages= 427–50 |year= 2006 |pmid= 16382100 |doi= 10.1124/pr.57.4.6 |s2cid=17936350 }}
* {{cite book | vauthors = Eder P, Poteser M, Groschner K | title = Transient Receptor Potential (TRP) Channels | chapter = TRPC3: A Multifunctional, Pore-Forming Signalling Molecule  | volume = 179 | issue = 179 | pages = 77–92 | year = 2007 | pmid = 17217051 | doi = 10.1007/978-3-540-34891-7_4 | isbn = 978-3-540-34889-4 | series = Handbook of Experimental Pharmacology }}
* {{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 = 1219–32 | date = April 2010 | pmid = 20345918 | doi = 10.1111/j.1460-9568.2010.07156.x | pmc=3036165}}
{{refend}}
== External links ==
* {{MeshName|TRPC3+protein,+human}}
{{NLM content}}
{{Ion channels|g4}}
{{Transient receptor potential channel modulators}}
{{DEFAULTSORT:Trpc3}}
[[Category:Ion channels]]
{{membrane-protein-stub}}