MODULATION OF THE DIHYDROPYRIDINE-SENSITIVE CALCIUM CHANNELS IN DROSOPHILA BY A PHOSPHOLIPASE C-MEDIATED PATHWAY

Disruption of phospholipase C-beta (PLC) by the norpA mutations of Dro sophila renders flies blind by affecting the light-evoked photorecepto r potential. We report here that the norpA-coded PLC modulates the 1,4 -dihydropyridine (DHP)-sensitive Ca2+ channels in lai val muscles. The DHP-sensitive current was reduced in the norpA mutants. Application o f 1 mu M phorbol 12-myristate 13-acetate (TPA) and 1 mu M phorbol 12,1 3-didecanoate (PDD), activators of protein kinase C (PKC), rescued the current in the mutant fibers without significantly affecting the norm al current. 4 alpha-phorbol 12,13-didecanoate (4 alpha PDD), an inacti ve analog of PDD, did not affect either the normal or the mutant curre nt. One micromolar bisindolylmaleimide (BIM), an inhibitor of PKC, red uced the current in the normal fibers without affecting the mutant cur rent. 300 mu M sn-1,2-dioctanoyl-glycerol (DOG), an analog of diacylgl ycerol (DAG), increased the current in the mutant fibers. These experi ments suggest that the DHP-sensitive Ca2+ channels in Drosophila may b e modulated by the PLC-DAG-PKC pathway, and that the same PLC isozyme which is involved in phototransduction in the adult flies may also mod ulate muscle Ca2+ channels in the larval stage of development. (C) 199 7 John Wiley & Sons, Inc. J Neurobiol.