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 Drosophila renders flies blind by affecting the light-evoked photoreceptor potential. We report here that the norpA-coded PLC modulates the 1,4-dihydropyridine (DHP)-sensitive Ca2+ channels in larval muscles. The DHP-sensitive current was reduced in the norpA mutants. Application of 1 microM phorbol 12-myristate 13-acetate (TPA) and 1 microM phorbol 12,13-didecanoate (PDD), activators of protein kinase C (PKC), rescued the current in the mutant fibers without significantly affecting the normal current. 4Alpha-phorbol 12,13-didecanoate (4alphaPDD), an inactive analog of PDD, did not affect either the normal or the mutant current. One micromolar bisindolylmaleimide (BIM), an inhibitor of PKC, reduced the current in the normal fibers without affecting the mutant current. 300 microM sn-1,2-dioctanoyl-glycerol (DOG), an analog of diacylglycerol (DAG), increased the current in the mutant fibers. These experiments suggest that the DHP-sensitive Ca2+ channels in Drosophila may be modulated by the PLC-DAG-PKC pathway, and that the same PLC isozyme which is involved in phototransduction in the adult flies may also modulate muscle Ca2+ channels in the larval stage of development.
Gu
G G
GG
Department of Biochemical Pharmacology, State University of New York at Buffalo, 14260-1200, USA.
Singh
S
S
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism; D004075:Diglycerides / Q000378:metabolism; D004095:Dihydropyridines / Q000494:pharmacology*; D004330:Drosophila / Q000737:chemistry* / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D007814:Larva / Q000737:chemistry / Q000201:enzymology; D008297:Male; D009132:Muscles / Q000737:chemistry / Q000201:enzymology; D009154:Mutation / Q000502:physiology; D011493:Protein Kinase C / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism*
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004075:Diglycerides; D004095:Dihydropyridines; D004791:Enzyme Inhibitors; C038806:1,4-dihydropyridine; D011493:Protein Kinase C; D010738:Type C Phospholipases