Role of TRP channels in endothelial pathophysiology—evidence for vascular TRPs as a potential target for drug therapy

Proteins related to the Drosophila transient receptor potential (TRP) gene product are key players in Ca2+ homeostasis of mammalian cells. TRP proteins form cation channels, which function as sensors for a variety of stimuli including oxidative stress. The canonical TRP proteins TRPC3 and TRPC4 are likely to play a role in endothelial physiology and pathophysiology. Here, we report that overexpression of TRPC3 or TRPC4 generates a redox-sensitive cation conductance in human embryonic kidney cells (HEK293). Redox activation of these TRPC species appears to be due to oxidant-induced promotion of phospholipase C activity and/or sensitisation of TRPC proteins to regulation by phospholipase C. Our results suggest TRPC species as attractive, novel targets for cardiovascular therapy. [Copyright &y& Elsevier]