POLYAMINE MODULATION OF EXCITATORY AMINO-ACID RESPONSES IN THE RAT CORTICAL WEDGE

Rat neocortex slices in Mg2+ free buffer show spontaneous discharges w hich have a constant frequency and are dependent on N-methyl-D-asparta te (NMDA) receptor activation. Spermine increased the frequency of dis charges at concentrations below 1 mM, had biphasic effects at 1 mM, an d only decreased the frequency of discharges at 3 mM. In contrast, the amplitude of these discharges was only reduced by spermine in a conce ntration dependent manner (300 muM to 3 mM). Spermidine produced simil ar effects, but was a less potent inhibitor of discharge frequency and amplitude than spermine. Diethylenetriamine (DET) 300 muM did not sig nificantly inhibit polyamine-induced increases in the discharge freque ncy. Polyamines inhibited direct depolarizations induced by the glutam ate agonists NMDA or alpha-amino-3-hydroxy-5-methyl-4-isoxazole propio nic acid (AMPA) in a concentration and time dependent manner. The data are consistent with two sites of action for polyamines, one enhancing the frequency of NMDA-mediated spontaneous epileptiform discharges an d the other inhibiting direct glutamate responses in rat cortex. The s low onset (time to maximal enhancement or inhibition by polyamines gre ater than 30 min) and lack of reversibility with polyamine removal sug gest that these sites are intracellular and/or presynaptic.