VALPROIC ACID INHIBITS THE DEPOLARIZING RECTIFICATION IN NEURONS OF RAT AMYGDALA

The actions of valproic acid (VPA) on neuronal membrane properties and synaptic transmission were studied using intracellular recording tech niques in rat basolateral neurons of the amygdala slices. In therapeut ically attainable concentrations (10-100 mu M), VPA decreased synaptic ally-induced epileptiform bursting in the presence of bicuculline. Add itionally, the frequency of repetitive discharge induced by direct sup erthreshold depolarizing current pulses was decreased by VPA. However, evoked excitatory and inhibitory postsynaptic potentials were not aff ected at this level of drug concentration. The current-voltage relatio nship of untreated neurons revealed rectification of membrane potentia l when neuronal membrane was depolarized with cathodal current pulses. This depolarizing rectification was blocked by VPA. High medium calci um or addition of the sodium channel blocker tetrodotoxin (TTX) also b locked the depolarizing rectification, whereas the calcium channel ant agonist diltiazem had no effect on the rectification. Elevation of med ium calcium concentration also blocked the bicuculline-induced burstin g. These results indicate that the inhibition by VPA of subthreshold s low sodium current and membrane depolarizing rectification results in suppression of neuronal membrane excitability which is probably a majo r mechanism for its anticonvulsant action.