TRPC4 channel

Channel name TRPC41,2,3,4,5,6,7,8
Description TRP receptor-operated channel
Other names TRP4, CCE1, bCCE
Molecular information Human unigene: Hs0.262960, chr. 13q13.1-q13.2
Mouse unigene: Mm0.10100, chr. 3
Associated subunits Forms homomeric channels in mouse; TRPC1, TRPC5
Functional assays Patch-clamp, calcium imaging
Current Nonselective, largely inward, double rectification
Conductance 41pS; unclear as homomer; estimates range from 18 to 40pS
Ion selectivity PNa/PCa = 1:1.1,2 1:73
Activation Activation of Gq-coupled receptors is known to activate TRPC4 current through activation of PLCβ
Inactivation Not established
Activators La3+ (100 μM) augments current
Gating inhibitors None
Blockers 2-APB, mM La3+, niflumic acid
Radioligands None
Channel distribution Brain, testis, placenta, adrenal gland, endothelium
Physiological functions Mediates agonist-dependent vasorelaxation in vascular endothelium
Mutations and pathophysiology Impaired agonist-dependent vasorelaxation in TRPC4 –/– mice
Pharmacological significance Possibly involved in signaling complexes
Comments Coexpression with TRPC1 or TRPC5 results in a novel NMDA-like voltage-dependent channel
  • chr., chromosome; NMDA, N-methyl-d-aspartate.

  • 1. Okada T, Shimizu S, Wakamori M, Maeda A, Kurosaki T, Takada N, Imoto K, and Mori Y (1998) Molecular cloning and functional characterization of a novel receptor-activated TRP Ca2+ channel from mouse brain. J Biol Chem 273:10279-10287

  • 2. Schaefer M, Plant TD, Obukhov AG, Hofmann T, Gudermann T, and Schultz G (2000) Receptor-mediated regulation of the nonselective cation channels TRPC4 and TRPC5. J Biol Chem 275:17517-17526

  • 3. Philipp S, Cavalié A, Freichel M, Wissenbach U, Zimmer S, Trost C, Marquart A, Murakami M, and Flockerzi V (1996) A mammalian capacitative calcium entry channel homologous to Drosophila TRP and TRPL. EMBO J 15:6166-6171

  • 4. Freichel M, Suh SH, Pfeifer A, Schweig U, Trost C, Weigerber P, Biel M, Philipp S, Freise D, Droogmans G, et al. (2001) Lack of an endothelial store-operated Ca2+ current impairs agonist-dependent vasorelaxation in TRP4–/– mice. Nat Cell Biol 3:121-127

  • 5. Tang Y, Tang J, Chen Z, Trost C, Flockerzi V, Li M, Ramesh V, and Zhu MX (2000) Association of mammalian trp4 and phospholipase C isozymes with a PDZ domain-containing protein, NHERF. J Biol Chem 275:37559-37564

  • 6. Strübing C, Krapivinsky G, Krapivinsky L, and Clapham DE (2001) TRPC1 and TRPC5 form a novel cation channel in mammalian brain. Neuron 29:645-655

  • 7. Strübing C, Krapivinsky G, Krapivinsky L, and Clapham DE (2003) Formation of novel TRPC channels by complex subunit interactions in embryonic brain. J Biol Chem 278:39014-39019

  • 8. Walker RL, Koh SD, Sergeant GP, Sanders KM, and Horowitz B (2002) TRPC4 currents have properties similar to the pacemaker current in interstitial cells of Cajal. Am J Physiol Cell Physiol 283:C1637-C1645