Regulation of TRPC6 Channels by non-steroid anti-inflammatory drugs

D. V. Ilatovskaya, T. S. Pavlov, Y. A. Negulyaev, A. Staruschenko

Research output: Contribution to journalArticlepeer-review


Family focal segmental glomerulosclerosis (FSGS) is characterized by sclerosis and hyalinosis of particular loops of glomeruli and is one of the causes of the nephrotic syndrome. Certain mutations in the structure of TRPC6 channels are the genetic impetus for the FSGS development resulting in podocytes functional abnormalities and various nephropathies. We have recently demonstrated that non-steroid anti-inflammatory drugs (NSAID) ibuprofen and diclofenac decrease the activity of endogenous TRPC-like cation channels in the podocytes of the freshly isolated rat glomeruli. It was also shown that TRPC6 channels are expressed in the podocytes. In the current study we functionally reconstituted TRPC6 channels in mammalian cells to investigate effects of diclofenac on the activity of wild type TRPC6 channel and TRPC6P112Q channel containing a mutation in the N-terminus that was described in FSGS patients. Intracellular calcium level measurements in transfected cells revealed a more intensive carbachol-induced increase of calcium concentration in HEK293 cells expressing TRPC6P112Q versus cells expressing wild-type TRPC6. We also performed patch-clamp experiments to study TRPC6 channels reconstituted in Chinese hamster ovarian (CHO) cell line and found that application of diclofenac (500 μM) acutely reduced single channel activity. Preincubation with diclofenac (100 μM) also decreased whole-cell current in CHO cells overexpressingTRPC6p112Q. Therefore, our previously published data about the effects of NSAID on TRPC-like channels in the isolated rat glomeruli, along with this current investigation on cultured overexpressed mammalian cells, allow hypothesizing that TRPC6 channels may be a target for NSAID that can be important in the treatment of FSGS.

Original languageEnglish (US)
Pages (from-to)200-208
Number of pages9
JournalBiologicheskie Membrany
Issue number3
StatePublished - 2012
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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