Short transient receptor potential channel 3 (TrpC3) also known astransient receptor protein 3 (TRP-3) is aprotein that in humans is encoded by theTRPC3gene. The TRPC3/6/7 subfamily are implicated in the regulation of vascular tone, cell growth, proliferation and pathological hypertrophy.[5] These are diacylglycerol-sensitivecation channels known to regulate intracellular calcium via activation of thephospholipase 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 ofTrkB byBDNF is TRPC3-dependent in the CNS.[8] TRPC channels are almost always co-localized withmGluR1-expressing cells and likely play a role in mGluR-mediatedEPSPs.[9]
The TRPC3 channel has been shown to be preferentially expressed in non-excitable cell types, such asoligodendrocytes.[6] However, evidence suggests that active TRPC3 channels inbasal 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 theaxon hillock, cell body, anddendritic processes of dopamine-expressing cells.[11]
The neuromodulator,substance P, activates TRPC3/7 channels inducing cellular currents that underlie rhythmic pacemaker activity in thebrainstem, 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.
A small molecule agonist isGSK1702934A and antagonists areGSK417651A and GSK2293017A.[5] A commercially available inhibitor is available in the form of a pyrazole compound, Pyr3[14] TRPC3 has been shown to specificallyinteract withTRPC1[15][16] andTRPC6.[17]
^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.PMID15245795.S2CID27636840.
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.
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.PMID16382100.S2CID17936350.
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.PMID17217051.
