TRPC4

Function

TrpC4 is a member of the transient receptor potential cation channels. This protein forms a non-selective calcium-permeable cation channel that is activated by Gαi-coupled receptors, Gαq-coupled receptors and tyrosine kinases, and plays a role in multiple processes including endothelial permeability, vasodilation, neurotransmitter release and cell proliferation.

Tissue distribution

The nonselective cation channel TrpC4 has been shown to be present in high abundance in the cortico-limbic regions of the brain. In addition, TRPC4 mRNA is present in midbrain dopaminergic neurons in the ventral tegmental area and the substantia nigra.

Roles

Deletion of the trpc4 gene decreases levels of sociability in a social exploration task. These results suggest that TRPC4 may play a role in regulating social anxiety in a number of different disorders. However deletion of the trpc4 gene had no impact on basic or complex strategic learning. Given that the trpc4 gene is expressed in a select population of midbrain dopamine neurons, it has been proposed that it may have an important role in dopamine related processes including addiction and attention.

Clinical significance

Single nucleotide polymorphisms in this gene may be associated with generalized epilepsy with photosensitivity.

Interactions

TRPC4 has been shown to interact with ITPR1, TRPC1, and TRPC5.

References

References

1. (May 1996). "trp, a novel mammalian gene family essential for agonist-activated capacitative Ca2+ entry". Cell.
2. (December 2005). "International Union of Pharmacology. XLIX. Nomenclature and structure-function relationships of transient receptor potential channels". Pharmacol. Rev..
3. "Entrez Gene: transient receptor potential cation channel, subfamily C, member 4".
4. (2007). "Corticolimbic expression of TRPC4 and TRPC5 channels in the rodent brain". PLOS ONE.
5. (2011). "Sociability is decreased following deletion of the trpc4 gene". Nature Precedings.
6. (2012). "Deletion of the trpc4 gene and its role in simple and complex strategic learning". Nature Precedings.
7. (2011). "TRPC4 ion channel protein is selectively expressed in a subpopulation of dopamine neurons in the ventral tegmental area". Nature Precedings.
8. (September 2010). "Association study of TRPC4 as a candidate gene for generalized epilepsy with photosensitivity". Neuromolecular Med..
9. (September 2003). "Homer binds TRPC family channels and is required for gating of TRPC1 by IP3 receptors". Cell.
10. (January 2001). "Alternative splice variants of hTrp4 differentially interact with the C-terminal portion of the inositol 1,4,5-trisphosphate receptors". FEBS Lett..
11. (October 2003). "Formation of novel TRPC channels by complex subunit interactions in embryonic brain". J. Biol. Chem..
12. (May 2002). "Subunit composition of mammalian transient receptor potential channels in living cells". Proc. Natl. Acad. Sci. U.S.A..