Spontaneous paroxysmal activity induced by zero magnesium and bicuculline: Suprression by NMDA antagonists and GABA mimetics

Abstract

Slices of rat cerebral cortex developed spontaneous paroxysmal discharges when superfused with Krebs medium containing zero Mg 2+ or 50 μM bicuculline. In both situations, the N-methyl-D-aspartate (NMDA) antagonists APV, 100 μM, and ketamine, 100 μM subsstantially reduced the frequency of the paroxysmal events, the reduction being greater in zero Mg 2+. γ-Aminobutyric acid (GABA) 1 mM, the GABA-A agonist muscimol 2 μM and the GABA-B receptor agonist baclofen 10 μM, each reduced the frequency of events in zero Mg 2+ while muscimol and GABA also reduced the amplitude of the events. GABA and baclofen were similarly effective against bicuculline-induced events but the muscimol concentration required was 5–10-fold higher. These results suggest that, under our vitro conditions, neocortical cells are normally restrained from paroxysmal discharges by Mg 2+. Inhibition by GABA through GABA-A receptors and inhibition by GABA through GABA-B receptors, may also contribute to this restraint.