Effects of valproate in a model nervous system (buccal ganglia of Helix pomatia): I. Antiepileptic actions.

Cellular actions of valproate (VPA) were studied using intracellular recordings of identified neuronal individuals in the buccal ganglia of Helix pomatia. Under nonepileptic conditions, VPA induced (a) a hyperpolarization, (b) slight changes in action potentials (AP), and (c) an increase in membrane resistance. Under epileptic conditions (i.e., during application of an epileptogenic drug), extracellular application of VPA decreased frequency of occurrence of epileptic depolarizations (early effect) and led to a decay in paroxysmal depolarizations (late effect). Intracellular injection of VPA could block epileptic activity in the treated neuron immediately. A metabolite of VPA (trans-2-en VPA) mainly lacked the late effect (decay in epileptic depolarizations) obtained with VPA. Results suggest that the early antiepileptic effect is exerted from the extracellular side of the neuronal membrane and that the late effect results from intracellular actions of VPA being delayed by slow access to an intracellular site.