Low-magnesium-induced epileptiform activity in the human neocortex maintained in vitro: Suppression by the organic calcium antagonist verapamil

Abstract

Animal experiments show that calcium currents essentially participate in epileptogenesis. Thus, epileptiform field potentials (EFP) were suppressed by organic calcium antagonists. Present investigations tested whether such an antiepileptic calcium antagonism also exists in human cerebral tissue. Experiments were performed on slices (400 μm) of human neocortex. Tissue used was a small portion of that which is normally removed for the treatment of brain tumor. Epileptiform activity was induced by superfusion with Mg 2+ -free cerebrospinal fluid (CSF). Verapamil (40 or 60 μmol/L) was added to the Mg 2+ -free CSF. Superfusion with Mg 2+ -free CSF induced epileptiform activity in the slices within half an hour. The EFP consisted of spikes or spike-wave complexes. The mean frequency of occurrence was 10 EFP/min. Application of verapamil led to an abolition of EFP within 1 and 2 h with 60 and 40 μmol/L verapamil, respectively. The suppressive effect was often preceded by a transient increase of frequency of occurrence of EFP. During washout of the organic calcium antagonist, EFP reappeared within 10 min. The observed antiepileptic calcium antagonism may offer the chance of a new strategy in pharmacotherapy of the epilepsies.