Last updated on: 18.12.2020

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TRPC is the acronym for "Transient Receptor Potential Cation Channel, Subfamily C". TRPCs represent a group of receptor-driven, calcium-permeable, non-selective cation channels of the TRP superfamily. Structurally, members of this family possess a number of similar features, including 3 or 4 ankyrin repeats near the N-terminus and a TRP box motif at the proximal C-terminus. Cryogenic electron microscopy was used to construct several high-resolution structures of TRPC channels with 3-D representations of the channel structures.

The channels are permeable to cations and contribute to a wide range of cellular functions and physiological roles. Their regulations have been shown to involve multiple components of the phospholipase C pathway, Gi and Go proteins, and internal Ca2+ stores. In general, TRPC channels can be activated by phospholipase C stimulation, although some members can also be activated by diacylglycerol.

TRPC 1,4 and 5 are activated by the metabotropic glutamate receptor 1 agonist dihydroxyphenylglycine. TRPC1 also by stretching cell membranes.

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The seven TRPC members can be divided into four subgroups based on their amino acid sequences and functional similarities:

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Role in cardiomyopathies: TRPC1 channels are found on cardiomyocytes, smooth muscle and endothelial cells (Rowell J et al. 2010). Up-regulation of TRPC1, TRPC3 and TRPC6 genes is observed in fibrotic heart disease as well as cardiovascular disease. TRPC channels are suspected to respond to an overload of hormonal and mechanical stimulation in cardiovascular disease and contribute to pathological remodelling of the heart (Rowell J et al. 2010). Apparently, TRPC1, TRPC3 and TRPC6 channels promote cardiac hypertrophy via activation of the calcineurin pathway and the downstream transcription factor nuclear factor of activated T cells (NFAT). In any case, deletion of the TRPC1 gene led to decreased hypertrophy in animal experiments when stimulated with hypertrophic stimuli. (Rowell J et al 2010). TRPC3 is upregulated in the atria of patients with atrial fibrillation (AF). Simultaneously, TRPC3 regulates angiotensin II-induced cardiac hypertrophy, which contributes to fibroblast formation. Blockade of TRPC3 results in a decrease in fibroblast formation and reduced susceptibility to AF.

There is strong evidence for the pathogenetic significance of mutations in the TRPC6 gene for familial focal segmental glomerulosclerosis.

Dysfunction of TRPC6 also seems to play a role in Alzheimer's disease (Lessard CB et al. 2005; Winn M P et al. 2005).

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The involvement of the TRPC channel in well-studied signaling pathways and its importance in the impact of genes on human disease make it a potential target for drug therapy (Moran M et al. 2011).

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  1. Boulay G et al. (1999) Modulation of Ca(2+) entry by polypeptides of the inositol 1,4, 5-trisphosphate receptor (IP3R) that bind transient receptor potential (TRP): evidence for roles of TRP and IP3R in store depletion-activated Ca(2+) entry. Proc Natl Acad Sci. U.S.A. 96: 14955-14960
  2. Fowler MA et al (2007) Corticolimbic expression of TRPC4 and TRPC5 channels in the rodent brain. PLoS ONE 2: e573.
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  8. Winn M P et al (2005) A mutation in the TRPC6 cation channel causes familial focal segmental glomerulosclerosis. Science 308: 1801-1804

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Last updated on: 18.12.2020