Dicarboxylic amino acids block epileptiform activity in hippocampal slice

Effects of prolonged (5-10 min) continuous perfusion of excitatory amino acids on penicillin (PEN)-evoked epileptiform activity in hippocampal slices were examined with extracellular and intracellular recordings. L-glutamate (GLU), L-aspartate (ASP), quisqualate (QUIS), and N-methyl-D,L-aspartate reversibly depressed multiple (epileptiform) population spikes elicited by PEN (1.7 mM). Intracellularly recorded, PEN-evoked paroxysmal depolarization shifts (PDS) were partially blocked by 1 mM GLU and largely eliminated by 2 mM GLU or ASP. In the presence of PEN, perfusion with both GLU and ASP induced a transient 4 to 6-mV depolarization, usually followed by spontaneous return of membrane potential to control levels. During the amino acid (AA)-induced block of epileptiform activity, there was no significant change in resting membrane potential, input resistance, or the ability to fire action potentials in response to depolarization, indicating that the decreased responsiveness is not a consequence of nonspecific pyramidal cell overdepolarization. The observed depression of epileptiform activity by continued exposure to GLU and its analogues may reflect desensitization or another regulatory mechanism to limit overexcitation.