title: Activation of TRP channels by protons and phosphoinositide depletion in Drosophila photoreceptors.
abstract: BACKGROUND
  Phototransduction 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, InsP(3) appears not to be involved, and recent studies have implicated lipid products of PLC activity, e.g., diacylglycerol, its metabolites, or the reduction in PIP(2). The fact that hydrolysis of the phosphodiester bond in PIP(2) by PLC also releases a proton is seldom recognized and has neither been measured in vivo nor implicated previously in a signaling context.
  
  
  RESULTS
  Following depletion of PIP(2) 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 (<10 ms) acidification originating in the microvilli, which is eliminated in mutants of PLC, and that heterologously expressed TRPL channels are activated by acidification of the cytosolic surface of inside-out patches.
  
  
  CONCLUSIONS
  Our results indicate that a combination of phosphoinositide depletion and acidification of the membrane/boundary layer is sufficient to activate the light-sensitive channels. Together with the demonstration of light-induced, PLC-dependent acidification, this suggests that excitation in Drosophila photoreceptors may be mediated by PLC's dual action of phosphoinositide depletion and proton release.
authors.affiliation: Department of Physiology, Development, and Neuroscience, Cambridge University, Cambridge CB2 3DY, UK.
authors.forename: Jiehong
authors.initials: J
authors.lastname: Huang
authors.forename: Che-Hsiung
authors.initials: CH
authors.lastname: Liu
authors.forename: Simon A
authors.initials: SA
authors.lastname: Hughes
authors.forename: Marten
authors.initials: M
authors.lastname: Postma
authors.forename: Christof J
authors.initials: CJ
authors.lastname: Schwiening
authors.forename: Roger C
authors.initials: RC
authors.lastname: Hardie
mesh_terms: D019297:2,4-Dinitrophenol / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D004330:Drosophila / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D029721:Drosophila Proteins / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D006863:Hydrogen-Ion Concentration; D010716:Phosphatidylinositols / Q000378:metabolism; D017785:Photons; D017956:Photoreceptor Cells, Invertebrate / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D050051:Transient Receptor Potential Channels / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D014785:Vision, Ocular / Q000502:physiology
chemical_list: D029721:Drosophila Proteins; D010716:Phosphatidylinositols; D050051:Transient Receptor Potential Channels; C063169:trp protein, Drosophila; C074192:trpl protein, Drosophila; D019297:2,4-Dinitrophenol