Activation of TRP Channels by Protons and Phosphoinositide Depletion in Drosophila Photoreceptors

SummaryBackgroundPhototransduction in microvillar photoreceptors is mediated via G protein-coupled phospholipase C (PLC), but how PLC activation leads to the opening of the light-sensitive TRPC channels (TRP and TRPL) remains unresolved. In Drosophila, InsP3 appears not to be involved, and recent studies have implicated lipid products of PLC activity, e.g., diacylglycerol, its metabolites, or the reduction in PIP2. The fact that hydrolysis of the phosphodiester bond in PIP2 by PLC also releases a proton is seldom recognized and has neither been measured in vivo nor implicated previously in a signaling context.ResultsFollowing depletion of PIP2 and other phosphoinositides by a variety of experimental manipulations, the light-sensitive channels in Drosophila photoreceptors become remarkably sensitive to rapid and reversible activation by the lipophilic protonophore 2-4 dinitrophenol in a pH-dependent manner. We further show that light induces a rapid (