ARACHIDONIC-ACID INHIBITS TRANSIENT POTASSIUM CURRENTS AND BROADENS ACTION-POTENTIALS DURING ELECTROGRAPHIC SEIZURES IN HIPPOCAMPAL PYRAMIDAL AND INHIBITORY INTERNEURONS

The transient outward potassium current was studied in outside-out mac ropatches excised from the soma of CA? pyramidal neurons and stratum ( st.) oriens-alveus inhibitory interneurons in rat hippocampal slices, Arachidonic acid dose dependently decreased the charge transfer associ ated with the transient current, concomitant with an increase in the r ate of current inactivation. Arachidonic acid (AA) did not affect the voltage dependence of steady state inactivation but did prolong the pe riod required for complete recovery from inactivation. The effects of AA were mimicked by the nonmetabolizable analog of AA, 5,8,11,14-eicos atetraynoic acid, suggesting that metabolic products of AA were not re sponsible for the observed blocking action, In addition, AA blocked st . oriensalveus-lacunosum-moleculare interneuron transient currents but not currents recorded from basket cell interneurons. In current clamp experiments, AA was without effect on the action potential waveform o f CA1 pyramidal neurons under control recording conditions. In voltage -clamp experiments, the use of a test pulse paradigm, designed to mimi c the action potential voltage trajectory, revealed that the transient current normally associated with a single spike deactivates too rapid ly for AA to have an effect. Transient currents activated by longer du ration ''action potential'' waveforms, however, were attenuated by AA. Consistent with this finding was the observation that AA broadened in terictal spikes recorded in the elevated [K+](o) model of epilepsy. Th ese data suggest that AA liberated from hippocampal neurons may act to block the transient current selectively in both CA1 pyramidal neurons and inhibitory interneurons and to broaden action potentials selectiv ely under pathological conditions.