Epileptiform events induced by GABA-antagonists in entorhinal cortical cells in vitro are partly mediated byN-methyl-d-aspartate receptors

Entorhinal cortical cells are susceptible to epileptogenesis induced by a reduction of GABAergic inhibition and the paroxysmal events contain a large, NMDA-receptor mediated component.

Abstract

The effects of the GABA-antagonists, picrotoxin and bicuculline on responses of medial entorhinal cortical cells to subicular stimulation were tested in vitro. On every cell tested either antagonist caused a profound enhancement of synaptically evoked depolarizations to the point where paroxysmal depolarizing shifts (PDS) were recorded, although only a minority of cells showed evidence of inhibitory potentials in the control situation. The initial PDS was followed by either a long afterdepolarization or a series of afterdischarges. The afterpotentials were always reduced or blocked by the N-methyl-D-aspartate (NMDA)-receptor antagonist, 2-amino-5-phosphonovalerate (2-AP5). The amplitude of the initial PDS in many cells was also reduced by 2-AP5. Thus, entorhinal cortical cells are susceptible to epileptogenesis induced by a reduction of GABAergic inhibition and the paroxysmal events contain a large, NMDA-receptor mediated component.