Arachidonic acid modulates hippocampal calcium current via protein kinase C and oxygen radicals.
Arachidonic acid (AA) is a second messenger liberated via receptor activation of phospholipase A2 or diacylglycerol-lipase. We used whole-cell voltage clamp of acutely isolated hippocampal CA1 pyramidal cells to investigate the hypothesis that AA modulates Ca2+ channel current (ICa) via activation of protein kinase C (PKC) and generation of free radicals. AA depressed ICa in a dose- and time-dependent manner similar to that previously reported for the action of phorbol esters on ICa. A similar depression was seen with a xanthine-based free radical generating system. The specific PKC inhibitor PKCI (19-36), the protein kinase inhibitor H-7, and the superoxide free radical scavenger SOD each blocked ICa depression by 70%-80%. Complete block of the AA response occurred when SOD was used simultaneously with a PKC inhibitor. These data suggest that PKC and free radicals play a role in AA-induced suppression of ICa.
Keyser
D O
DO
Department of Physiology, University of Maryland School of Medicine, Baltimore 21201.
Alger
B E
BE
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000502:physiology*; D002118:Calcium / Q000502:physiology*; D004594:Electrophysiology; D005609:Free Radicals; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D009637:Masoprocol / Q000494:pharmacology; D009474:Neurons / Q000502:physiology; D010100:Oxygen / Q000502:physiology*; D011493:Protein Kinase C / Q000502:physiology*; D013482:Superoxide Dismutase / Q000494:pharmacology
D001095:Arachidonic Acids; D005609:Free Radicals; D016718:Arachidonic Acid; D009637:Masoprocol; D013482:Superoxide Dismutase; D011493:Protein Kinase C; D010100:Oxygen; D002118:Calcium