Phospholipase C activates protein kinase C during induction of slow Na current in Xenopus oocytes.
Protein phosphorylation by protein kinase C (PKC) has recently been shown to be a key event in the induction of the slow inward Na current observed during sustained depolarization of the Xenopus oocyte membrane. The present work investigates the possible pathways leading to PKC activation. PKC is activated by a series of phospholipid metabolites, such as diacylglycerol (DAG) and arachidonic acid produced by phospholipases C (PLC) and A2 (PLA2) respectively. To test whether PKC activation was dependent upon the phospholipid metabolites produced either by PLC or by PLA2, enzyme activity was reduced using selective inhibitors. Results indicated that inhibition of PLA2 activity and inhibition of the enzymes involved in the arachidonic acid cascade failed to affect Na current amplitude. On the other hand, PLC inhibition caused a marked decrease of Na current amplitude. In another series of experiments, Na current was fully restored, in spite of PLC inhibition, by directly enhancing PKC activity with a powerful activator phorbol 12-myristate 13-acetate. These data strongly suggest that PLC is involved in PKC activation during Na channel induction.
Charpentier
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G
Laboratoire de Neurobiologie Cellulaire, Université de Picardie Jules Verne, Faculté des Sciences, Amiens, France.
Béhue
N
N
Fournier
F
F
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism / Q000494:pharmacology; D004075:Diglycerides / Q000378:metabolism / Q000494:pharmacology; D004789:Enzyme Activation; D005260:Female; D009355:Neomycin / Q000494:pharmacology; D009865:Oocytes / Q000187:drug effects / Q000502:physiology*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D026941:Sodium Channel Blockers; D015222:Sodium Channels / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014982:Xenopus laevis
D004075:Diglycerides; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D016718:Arachidonic Acid; D011493:Protein Kinase C; D010738:Type C Phospholipases; D009355:Neomycin; D013755:Tetradecanoylphorbol Acetate