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 TRPC3gene. 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]
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.
Modulatorsedit
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]
^ abcGRCh38: Ensembl release 89: ENSG00000138741 - Ensembl, May 2017
^ abcGRCm38: 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.
^ abXu 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.
^ abFusco 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. PMC3652281. 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. ISBN978-1-4398-1860-2. 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. PMC3036165. 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. PMC4362401. 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. PMC2664023. 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. PMC124253. PMID 12032305.
Further readingedit
Islam, Md. Shahidul (January 2011). Transient Receptor Potential Channels. Advances in Experimental Medicine and Biology. Vol. 704. Berlin: Springer. p. 700. ISBN978-94-007-0264-6.
Lemmon MA (March 2005). "Pleckstrin homology domains: two halves make a hole?". Cell. 120 (5): 574–6. doi:10.1016/j.cell.2005.02.023. PMID 15766521. S2CID 16696677.
Clapham DE, Julius D, Montell C, Schultz G (2006). "International Union of Pharmacology. XLIX. Nomenclature and structure-function relationships of transient receptor potential channels". Pharmacol. Rev. 57 (4): 427–50. doi:10.1124/pr.57.4.6. PMID 16382100. S2CID 17936350.
Eder P, Poteser M, Groschner K (2007). "TRPC3: A Multifunctional, Pore-Forming Signalling Molecule". Transient Receptor Potential (TRP) Channels. Handbook of Experimental Pharmacology. Vol. 179. pp. 77–92. doi:10.1007/978-3-540-34891-7_4. ISBN978-3-540-34889-4. PMID 17217051.
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. PMC3036165. PMID 20345918.
trpc3, short, transient, receptor, potential, channel, trpc3, also, known, transient, receptor, protein, protein, that, humans, encoded, gene, subfamily, implicated, regulation, vascular, tone, cell, growth, proliferation, pathological, hypertrophy, these, dia. 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 TRPC3IdentifiersAliasesTRPC3 SCA41 TRP3 transient receptor potential cation channel subfamily C member 3External IDsOMIM 602345 MGI 109526 HomoloGene 20708 GeneCards TRPC3Gene location Human Chr Chromosome 4 human 1 Band4q27Start121 874 481 bp 1 End121 952 060 bp 1 Gene location Mouse Chr Chromosome 3 mouse 2 Band3 B 3 17 93 cMStart36 674 631 bp 2 End36 744 316 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed insecondary oocyteendothelial cellpituitary glandanterior pituitarygastric mucosaputamenganglionic eminenceprefrontal cortexstromal cell of endometriumcaudate nucleusTop expressed incerebellar vermismedial dorsal nucleuslateral geniculate nucleusmedial geniculate nucleusmedial vestibular nucleussuperior colliculussuperior frontal gyrusglobus palliduspineal glanddorsal tegmental nucleusMore reference expression dataBioGPSMore reference expression dataGene ontologyMolecular functionstore operated calcium channel activity calcium channel activity inositol 1 4 5 trisphosphate binding ion channel activity protein bindingCellular componentintegral component of membrane membrane plasma membrane integral component of plasma membrane cation channel complexBiological processresponse 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 concentrationSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez722222065EnsemblENSG00000138741ENSMUSG00000027716UniProtQ13507Q9QZC1RefSeq mRNA NM 001130698NM 003305NM 001366479NM 019510RefSeq protein NP 001124170NP 003296NP 001353408n aLocation UCSC Chr 4 121 87 121 95 MbChr 3 36 67 36 74 MbPubMed search 3 4 WikidataView Edit HumanView Edit Mouse Contents 1 Function 2 Modulators 3 See also 4 References 5 Further reading 6 External linksFunction editNon 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 editA 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 editTransient receptor potential channel TRPCReferences edit 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 Giampa 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 Giampa 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 amp 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 Wolkart 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 Strubing 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 Further reading editIslam Md Shahidul January 2011 Transient Receptor Potential Channels Advances in Experimental Medicine and Biology Vol 704 Berlin Springer p 700 ISBN 978 94 007 0264 6 Lemmon MA March 2005 Pleckstrin homology domains two halves make a hole Cell 120 5 574 6 doi 10 1016 j cell 2005 02 023 PMID 15766521 S2CID 16696677 Clapham DE Julius D Montell C Schultz G 2006 International Union of Pharmacology XLIX Nomenclature and structure function relationships of transient receptor potential channels Pharmacol Rev 57 4 427 50 doi 10 1124 pr 57 4 6 PMID 16382100 S2CID 17936350 Eder P Poteser M Groschner K 2007 TRPC3 A Multifunctional Pore Forming Signalling Molecule Transient Receptor Potential TRP Channels Handbook of Experimental Pharmacology Vol 179 pp 77 92 doi 10 1007 978 3 540 34891 7 4 ISBN 978 3 540 34889 4 PMID 17217051 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 External links editTRPC3 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 nbsp This membrane protein related article is a stub You can help Wikipedia by expanding it vte Retrieved from https en wikipedia org w index php title TRPC3 amp oldid 1144593440, wikipedia, wiki, book, books, library,
