TRPC1

TRPC1 is the acronym for Transient Receptor Potential Cation Channel Subfamily C Member 1.
TRPCs represent a group of receptor-driven, calcium-permeable, non-selective transmembrane 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. 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.

TRP channels are phylogenetically early signaling pathways (they can already be detected in yeast cells). The first TRP channel was identified in 1989 in connection with visual perception in Drosophila melanogaster. In a Drosophila mutant (trp343), it was shown that its photoreceptors responded to light stimuli only with a transient, i.e. rapidly inactivating, membrane current. In the non-mutated wild type, however, the current flow persisted as long as light hit the photoreceptor. The mutant protein -TRP- was cloned in 1989. Thus, the name "transient receptor potential" - TRP- refers to the description of a phenotype of a mutant of the fruit fly Drosophila melanogaster. TRP channels exert important functions in primary signaling pathways for the regulated influx of Ca2+ into a cell in both vertebrates and non-vertebrates. TRP channels in humans play an important role in the sensation of different types of taste (sweet, bitter, umami) as well as in the perception of pain, heat, warmth or cold, pressure and light. It is believed that some TRP channels in the body behave like microscopic thermosensors. To date, 28 TRP channel genes have been identified in mammals (Nilius B et al. 2011). The TRPC subfamily consists of seven members (TRPC1-7) known to be non-selective cation channels with permeability to Ca2+, Na+ and K+.

Role in cardiomyopathies: TRPC1 channels are expressed 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).

Antagonists for TRPC1, TRPC4 and TRPC5 have been described to include clemizole and galangin.

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).

1. Ahmmed GU et al (2010) Protein kinase Calpha phosphorylates the TRPC1 channel and regulates store-operated Ca2+ entry in endothelial cells. The Journal of biological chemistry
2. Fowler MA et al (2007) Corticolimbic expression of TRPC4 and TRPC5 channels in the rodent brain. PLoS ONE 2: e573.
3. Lessard CB et al (2005) The overexpression of presenilin2 and Alzheimer's disease-linked presenilin2 variants influences TRPC6-enhanced Ca2+ entry into HEK293 cells. Cell Signal 17: 437-445.
4. Nilius B et al (2011) The transient receptor potential family of ion channels. Genome Biol 12:218.
5. Nilius B et al. 2007). Transient receptor potential cation channels in disease. Physiol Rev 87: 165-217.
6. Rowell J et al. (2010) TRP-ing up heart and vessels: canonical transient receptor potentials and cardiovascular disease. Journal of Cardiovascular Translational Research3: 516-524.
7. Wes PD et al. (1995) TRPC1, a human homolog of a Drosophila store-operated channel. Proceedings of the National Academy of Sciences of the United States of America 23.