Effects of anticonvulsants on spontaneous epileptiform activity which develops in the absence of chemical synaptic transmission in hippocampal slices

Spontaneous epileptiform activity (SEA) develops in area CA1 of hippocampal slices, when the Ca²⁺ concentration in the perfusate is lowered to 0.2 mM, at which level evoked chemical synaptic transmission is blocked. We investigated the effects of different anticonvulsants on this autonomous activity, in order to determine whether the antiepileptic effect can be ascribed to an influence on neuronal excitability. Carbamazepine was the most effective to block SEA at concentrations of 1-15 μM. Phenobarbital and phenytoin depressed SEA at concentrations of 25 μM. Valproate was effective at concentrations of 2-5 mM. Midazolam, a water-soluble benzodiazepine agonist and the N-methyl-d-aspartate antagonists, d-α-aminoadipic acid and 2-amino-7-phosphonoheptanoic acid were ineffective in blocking SEA suggesting that they exert their antiepileptic action by interference with synaptic mechanisms.