Arachidonic acid modulates hippocampal calcium current via protein kinase C and oxygen radicals

• Published in: Neuron (Cambridge, Mass.) Vol. 5; no. 4; pp. 545 - 553
• Main Authors: Keyser, D.O., Alger, B.E.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.1990
• Subjects: Animals; Arachidonic Acid; Arachidonic Acids - physiology; Calcium - physiology; Electrophysiology; Free Radicals; Hippocampus - cytology; Hippocampus - physiology; Masoprocol - pharmacology; Neurons - physiology; Oxygen - physiology; Protein Kinase C - physiology; Rodentia; Superoxide Dismutase - pharmacology
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/0896-6273(90)90092-T

Arachidonic acid (AA) is a second messenger liberated via receptor activation of phospholipase A 2 or diacylglycerol-lipase. We used whole-cell voltage clamp of acutely isolated hippocampal CA1 pyramidal cells to investigate the hypothesis that AA modulates Ca 2+ channel current (I Ca) via activation of protein kinase C (PKC) and generation of free radicals. AA depressed I Ca in a dose- and time-dependent manner similar to that previously reported for the action of phorbol esters on I Ca. 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 I Ca 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 I Ca.