Depolarization and activation of dihydropyridine-sensitive Ca2+ channels stimulate inositol phosphate accumulation in photoreceptor-enriched chick retinal cell cultures.
Elevated concentrations of extracellular K+ increased inositol phosphate accumulation in primary cultures of chick retinal photoreceptors and multipolar neurons. K+-evoked stimulation of inositol phosphate accumulation was greater in photoreceptor-enriched cell cultures than in cultures where multipolar neurons were the predominant cell type. Destroying multipolar neurons, but not photoreceptors, with kainic acid and N-methyl-D-aspartate did not reduce the K+-evoked stimulation of inositol phosphate accumulation. Both of these observations indicate that the observed effects occur in photoreceptor cells. The K+-evoked stimulation of inositol phosphate accumulation was blocked by omitting Ca2+ from the incubation medium or by adding the dihydropyridine-sensitive Ca2+-channel antagonists, nitrendipine and nifedipine. Bay K 8644, a dihydropyridine agonist, stimulated inositol phosphate accumulation and enhanced the effect of K+. omega-Conotoxin GVIA, an inhibitor of N-type Ca2+ channels, had no significant effect on K+-stimulated inositol phosphate accumulation. Pretreatment with pertussis toxin neither blocked K+-evoked inositol phosphate accumulation nor altered the inhibitory effect of nifedipine. K+-evoked inositol phosphate accumulation appears to reflect activation of phosphatidylinositol-specific phospholipase C, as it is inhibited by U-73122. These results indicate that Ca2+ influx through voltage-gated, dihydropyridine-sensitive channels activates phospholipase C in photoreceptor inner segments and/or synaptic terminals.
Gan
J
J
Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia 30322-3090, U.S.A.
Iuvone
P M
PM
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000502:physiology*; D002478:Cells, Cultured; D002642:Chick Embryo; D004095:Dihydropyridines / Q000494:pharmacology*; D004558:Electric Stimulation; D004963:Estrenes / Q000494:pharmacology; D007295:Inositol Phosphates / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009543:Nifedipine / Q000494:pharmacology; D037342:Pertussis Toxin; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010786:Photoreceptor Cells / Q000737:chemistry* / Q000166:cytology / Q000201:enzymology; D011188:Potassium / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004095:Dihydropyridines; D004963:Estrenes; D007295:Inositol Phosphates; D019269:Phosphatidylinositol 4,5-Diphosphate; D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; D010566:Virulence Factors, Bordetella; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; C038806:1,4-dihydropyridine; D037342:Pertussis Toxin; D010738:Type C Phospholipases; D009543:Nifedipine; D011188:Potassium; D002118:Calcium