Regulation Of Trpc6 Channel By Hydrogen Peroxide

The present study was performed to examine the effect of H 2 O 2 on TRPC6 channel in HEK293t cells. In the TRPC6 expressing cells, H 2 O 2 significantly stimulated Ca 2+ entry in a dose‐dependent manner. This effect appeared through a distinct mechanism from DAG because the Ca 2+ entry response and TRPC6 channel activity induced by a combination of OAG and H 2 O 2 was significantly greater than the individual response of either OAG or H 2 O 2 . Inhibition of endogenous H 2 O 2 by catalase substantially attenuated the OAG‐induced Ca 2+ entry. NEM, a thiol‐specific oxidizing agent, were able to mimic the H 2 O 2 response, and DTT, a thiol‐specific reducing agent, significantly inhibited the H 2 O 2 response. DTNB, a cell membrane‐impermeable thiol oxidizing agent, did not affect TRPC6 channel activity when applied via the pipette solution in cell‐attached patches. Furthermore, the NEM‐induced TRPC6 activation was only observed in cell‐attached patches, but not in inside‐out patches. Taken together, these data indicate that H 2 O 2 is an activator of TRPC6 channel. This H 2 O 2 dependent response is through modification of thiol groups on intracellular proteins. Funding was provided by the American Diabetes Association.