Kynuretic acid blocks spontaneous epileptiform bursts induced by 4-aminopyridine in rat amygdala neurons.

The effects of excitatory amino acid receptor antagonists, kynuretic acid and DL-2-amino-5-phosphonovalerate (DL-APV), on spontaneous epileptiform activity induced by 4-aminopyridine (4-AP) were studied in rat amygdala slices using intracellular recording techniques. Five to ten minutes after switching to 4-AP containing solution, spontaneous epileptiform bursts were observed in 37 out of 48 slices studied. The spontaneous epileptiform events consisted of an initial burst followed by a number of afterdischarges. Superfusion with kynuretic acid, a nonspecific excitatory amino acid receptor antagonist, reversibly reduced the duration of the spontaneous bursting discharges in a dose-dependent manner. The frequency of spontaneous bursting was also decreased. The IC50, estimated from the graph of the concentration-response relationship, was approximately 130 microM. In contrast to kynuretic acid, DL-APV, which is a specific N-methyl-D-aspartate (NMDA) receptor antagonist, failed to block the spontaneous bursting. These results suggest that activation of excitatory amino acid receptors of non-NMDA type is involved in the generation of propagation of spontaneous epileptiform events induced by 4-AP in the neurons of basolateral amygdala.