ARACHIDONIC-ACID ACTIVATION OF POTASSIUM CHANNELS IN RAT VISUAL-CORTEX NEURONS

We investigated the effects of arachidonic acid on K+ channels in fres hly dissociated neurons of 10- to 20-day-old rat visual cortex, using a perforated and conventional whole-cell patch-clamp and inside-out ex cised patch configurations. Arachidonic acid at 5-30 mu M induced an o utward current in 88.1% of the neurons in a hole-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+ channe ls were partially blocked by extracellular administration of 1 mM tetr aethylammonium and 100 nM charybdotoxin. However, Ba2+ completely bloc ked the channel in all cases. None of the other K+ channel blockers, i ncluding 4-aminopyridine, quinidine, apamin and glibenclamide, inhibit ed the arachidonic acid-activated channels. Intracellular perfusion wi th Ca2+-free and 5 mM BAPTA in Ca2+-free extracellular perfusate conta ining 2 mM EGTA in conventional whole-cell recording did not inhibit t he K+ channel, implying that the channel is not Ca2+ dependent. Neithe r guanosine 5'-O-(2-thiodiphosphate) nor staurosporine applied in insi de-out mode affected the arachidonic acid-activated channels, indicati ng that G-protein and protein kinase C are not involved in this phenom enon. In addition, neither indomethacin nor nordihydroguaiaretic acid blocked the channel currents, demonstrating that it is arachidonic aci d itself but not its metabolites that induced the effect. Among the fa tty acids tested, only cis-unsaturated fatty acids, having more than t wo double bonds, such as arachidonic acid, docosahexaenoic acid and li nolenic acid, activated the K+ channels. These findings suggest that t here exists a novel type of K+ channel activated by arachidonic acid w hich may play a critical role in modulating neuronal excitability in c ortical neurons. (C) 1997 IBRO. Published by Elsevier Science Ltd.