Extracellular Magnesium and Anticonvulsant Effects of Valproate in Young Rat Hippocampus

Summary Extracellular field potential recordings were made in CA3 subfield of hippocampal slices from rats aged 11–22 days. In these experiments, we analyzed the effects induced by modifying [Mg 2+ ] in the medium (1 or 2 mM) on (a) 4‐aminopyridine (4‐AP, 50 μM)‐induced synchronous events (including ictal‐ and interictal‐like epileptiform discharges as well as γ‐aminobutyric acid (GABA)‐mediated potentials), and (b) the changes induced by the antiepileptic drug (AED) valproate (VPA 2 mM) on such activities. Changing [Mg 2+ ] from 1 to 2 mM induced age‐dependent effects consisting of reduction in rate of occurrence of ictal‐like discharges at 11–13 days (55% reduction, p <0.005) and 14–16 days (46% reduction, p <0.025) postpartum. At any age, the rate of occurrence and the amplitude of the GABA‐mediated synchronous potentials tended to decrease in 1 mM [Mg 2+ ] Similar effects were noted when changes in [Mg 2+ ] were made during continuous application of the competitive antagonist of the N ‐methyl‐D‐aspartate (NMDA) receptor DL‐2‐amino‐5‐phosphonovalerate (APV 50 μM). As previously reported, interictal and ictal discharges were blocked by addition of VPA to medium containing 2 mM [Mg 2+ ] Such an effect was not observed when [Mg 2+ ] was decreased to 1 m M. In 1 m M , but not in 2 m M [Mg 2+ ], VPA increased the amplitude of GABA‐mediated synchronous potentials. Our results indicate that [Mg 2+ ] plays a role in modulating occurrence of 4‐AP‐induced ictal activity and that it can influence the effects of VPA in this in vitro model of epileptogenesis. Because these findings are also observed in the presence of the NMDA receptor antagonist APV, we conclude that they are nof mediated by a mechanism linked to the NMDA receptor‐ionophore.