Epileptiform events induced by GABA-antagonists in entorhinal cortical cells in vitro are partly mediated by N-methyl-D-aspartate receptors.
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.
D015763:2-Amino-5-phosphonovalerate; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D004827:Epilepsy / Q000139:chemically induced* / Q000378:metabolism; D066298:In Vitro Techniques; D010852:Picrotoxin / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology*; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology
D015763:2-Amino-5-phosphonovalerate; D001640:Bicuculline; D010852:Picrotoxin; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D014633:Valine