Arachidonic acid activation of potassium channels in rat visual cortex neurons

We investigated the effects of arachidonic acid on K+ channels in freshly dissociated neurons of 10- to 20-day-old rat visual cortex, using a perforated and conventional whole-cell patch-clamp and inside-out excised patch configurations. Arachidonic acid at 5-30 microM induced an outward current in 88.1% of the neurons in whole-cell mode, and evoked channel opening with a conductance of 170-238 pS in 90.5% of neurons under inside-out patch recording. Arachidonic acid-activated K+ channels were partially blocked by extracellular administration of 1 mM tetraethylammonium and 100 nM charybdotoxin. However, Ba2+ completely blocked the channel in all cases. None of the other K+ channel blockers, including 4-aminopyridine, quinidine, apamin and glibenclamide, inhibited the arachidonic acid-activated channels. Intracellular perfusion with Ca2+-free and 5 mM BAPTA in Ca2+-free extracellular perfusate containing 2 mM EGTA in conventional whole-cell recording did not inhibit the K+ channel, implying that the channel is not Ca2+ dependent. Neither guanosine 5'-O-(2-thiodiphosphate) nor staurosporine applied in inside-out mode affected the arachidonic acid-activated channels, indicating that G-protein and protein kinase C are not involved in this phenomenon. In addition, neither indomethacin nor nordihydroguaiaretic acid blocked the channel currents, demonstrating that it is arachidonic acid itself but not its metabolites that induced the effect. Among the fatty acids tested, only cis-unsaturated fatty acids, having more than two double bonds, such as arachidonic acid, docosahexaenoic acid and linolenic acid, activated the K+ channels. These findings suggest that there exists a novel type of K+ channel activated by arachidonic acid which may play a critical role in modulating neuronal excitability in cortical neurons.