Oxidative downmodulation of the transient K-current I-A by intracellular arachidonic acid in rat hippocampal neurons

Membrane-permeable arachidonic acid (AA) is liberated in a Ca2+-dependent w ay inside cells. By using whole cell patch clamp we show that intracellular AA (1 pM) selectively reduces I-A in rat hippocampal neurons, whereas extr acellular application requires a 10(6)-fold concentration. The nonmetaboliz ed AA analogue ETYA mimics the effect of AA that is blocked by ascorbic aci d or intracellular glutathione, suggesting an intracellular oxidative mecha nism. We conclude that intracellular AA is extremely potent in reducing I-A by an oxidative mechanism, particularly during oxidative stress.