Metabolic stress reversibly activates the Drosophila light-sensitive channels TRP and TRPL in vivo

Drosophila transient receptor potential (TRP) is a prototypical member of a novel family of channel proteins underlying phosphoinositide-mediated Ca2 entry. Although the initial stages of this signaling cascade are well know n, downstream events leading to the opening of the TRP channels are still o bscure. In the present study we applied patch-clamp whole-cell recordings a nd measurements of Ca2+ concentration by ion-selective microelectrodes in e yes of normal and mutant Drosophila to isolate the TRP and TRP-like (TRPL)- dependent currents. We report that anoxia rapidly and reversibly depolarize s the photoreceptors and induces Ca2+ influx into these cells in the dark. We further show that openings of the light-sensitive channels, which mediat e these effects, can be obtained by mitochondrial uncouplers or by depletio n of ATP in photoreceptor cells, whereas the effects of illumination and al l forms of metabolic stress were additive. Effects similar to those found i n wild-type flies were also found in mutants with strong defects in rhodops in, Gq-protein, or phospholipase C, thus indicating that the metabolic stre ss operates at a late stage of the phototransduction cascade. Genetic elimi nation of both TRP and TRPL channels prevented the effects of anoxia, mitoc hondrial uncouplers, and depletion of ATP, thus demonstrating that the TRP and TRPL channels are specific targets of metabolic stress. These results s hed new light on the properties of the TRP and TRPL channels by showing tha t a constitutive ATP-dependent process is required to keep these channels c losed in the dark, a requirement that would make them sensitive to metaboli c stress.