The effect of omega-3 fatty acids on Ca-ATPase in rat cerebral cortex

Neuronal Ca-ATPase has the essential function of keeping intracellular Ca levels in the micromolar range. This is a prerequisite for normal neurotransmission. This study was designed to determine whether Ca-ATPase is a target for docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) action: results show that both these fatty acids are inhibitors of Ca-ATPase activity in synaptosomal membranes isolated from rat cerebral cortex (-65 +/- 5% at [DHA] = 20 mug/ml, -59 +/- 7% at [EPA] = 20 mug/ml). The inhibition caused by EPA, but not that of DHA, could be reversed completely by the addition of calphostin, a protein kinase C blocker. In contrast, DHA could stimulate Ca-ATPase activity (+ 132 +/- 5% at [DHA] = 30 mug/ml) only in calmodulin-depleted membranes. In addition, Na,K-ATPase (which drives the Na-Ca exchanger) was inhibited by both DHA and EPA, both at 30 mug/ml (-15 +/- 0.7% and -42 +/- 1%, respectively). These results suggest a mechanism that explains the dampening effect of omega-3 fatty acids on neuronal activity. (C) 2002 Elsevier Science Ltd. All rights reserved.