Oxidative Downmodulation of the Transient K-CurrentI A by Intracellular Arachidonic Acid in Rat Hippocampal Neurons

Membrane-permeable arachidonic acid (AA) is liberated in a Ca2+-dependent way inside cells. By using whole cell patch clamp we show that intracellular AA (1 pM) selectively reduces I A in rat hippocampal neurons, whereas extracellular application requires a 106-fold concentration. The nonmetabolized AA analogue ETYA mimics the effect of AA that is blocked by ascorbic acid or intracellular glutathione, suggesting an intracellular oxidative mechanism. We conclude that intracellular AA is extremely potent in reducing I A by an oxidative mechanism, particularly during oxidative stress.