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Transient receptor potential cation channel, subfamily C, member 6, also known as TRPC6, is a human gene encoding a protein of the same name. TRPC6 is a transient receptor potential ion channel. It has been associated with depression and anxiety (see below), as well as with focal segmental glomerulosclerosis (FSGS).[1]


TRPC6 has been shown to interact with:


Two of the primary active constituents responsible for the antidepressant and anxiolytic benefits of Hypericum perforatum, also known as St. John's Wort, are hyperforin and adhyperforin.[5][6] These compounds are inhibitors of the reuptake of serotonin, norepinephrine, dopamine, γ-aminobutyric acid, and glutamate, and they are reported to exert these effects by binding to and activating TRPC6.[6][7] Recent results with hyperforin have cast doubt on these findings as similar currents are seen upon Hyperforin treatment regardless of the presence of TRPC6.[8]


  1. Winn MP, Conlon PJ, Lynn KL, Farrington MK, Creazzo T, Hawkins AF, Daskalakis N, Kwan SY, Ebersviller S, Burchette JL, Pericak-Vance MA, Howell DN, Vance JM, Rosenberg PB (June 2005). "A mutation in the TRPC6 cation channel causes familial focal segmental glomerulosclerosis". Science. 308 (5729): 1801–4. doi:10.1126/science.1106215. PMID 15879175.
  2. Hisatsune C, Kuroda Y, Nakamura K, Inoue T, Nakamura T, Michikawa T, Mizutani A, Mikoshiba K (April 2004). "Regulation of TRPC6 channel activity by tyrosine phosphorylation". The Journal of Biological Chemistry. 279 (18): 18887–94. doi:10.1074/jbc.M311274200. PMID 14761972.
  3. Chu X, Tong Q, Cheung JY, Wozney J, Conrad K, Mazack V, Zhang W, Stahl R, Barber DL, Miller BA (March 2004). "Interaction of TRPC2 and TRPC6 in erythropoietin modulation of calcium influx". The Journal of Biological Chemistry. 279 (11): 10514–22. doi:10.1074/jbc.M308478200. PMID 14699131.
  4. Hofmann T, Schaefer M, Schultz G, Gudermann T (May 2002). "Subunit composition of mammalian transient receptor potential channels in living cells". Proceedings of the National Academy of Sciences of the United States of America. 99 (11): 7461–6. doi:10.1073/pnas.102596199. PMC 124253. PMID 12032305.
  5. Müller WE, Singer A, Wonnemann M (July 2001). "Hyperforin--antidepressant activity by a novel mechanism of action". Pharmacopsychiatry. 34 Suppl 1: S98–102. doi:10.1055/s-2001-15512. PMID 11518085.
  6. 6.0 6.1 Chatterjee SS, Bhattacharya SK, Wonnemann M, Singer A, Müller WE (1998). "Hyperforin as a possible antidepressant component of hypericum extracts". Life Sciences. 63 (6): 499–510. doi:10.1016/S0024-3205(98)00299-9. PMID 9718074.
  7. Leuner K, Kazanski V, Müller M, Essin K, Henke B, Gollasch M, Harteneck C, Müller WE (December 2007). "Hyperforin--a key constituent of St. John's wort specifically activates TRPC6 channels". FASEB Journal. 21 (14): 4101–11. doi:10.1096/fj.07-8110com. PMID 17666455.
  8. Sell TS, Belkacemi T, Flockerzi V, Beck A (December 2014). "Protonophore properties of hyperforin are essential for its pharmacological activity". Scientific Reports. 4: 7500. doi:10.1038/srep07500. PMC 4266863. PMID 25511254.

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