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 techniques in rat basolateral neurons of the amygdala slices. In therapeutically attainable concentrations (10-100 microM), VPA decreased synaptically-induced epileptiform bursting in the presence of bicuculline. Additionally, the frequency of repetitive discharge induced by direct superthreshold depolarizing current pulses was decreased by VPA. However, evoked excitatory and inhibitory postsynaptic potentials were not affected at this level of drug concentration. The current-voltage relationship of untreated neurons revealed rectification of membrane potential when neuronal membrane was depolarized with cathodal current pulses. This depolarizing rectification was blocked by VPA. High medium calcium or addition of the sodium channel blocker tetrodotoxin (TTX) also blocked the depolarizing rectification, whereas the calcium channel antagonist diltiazem had no effect on the rectification. Elevation of medium calcium concentration also blocked the bicuculline-induced bursting. These results indicate that the inhibition by VPA of subthreshold slow sodium current and membrane depolarizing rectification results in suppression of neuronal membrane excitability which is probably a major mechanism for its anticonvulsant action.
Tian
L M
LM
Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, TX 77204-5515.
Alkadhi
K A
KA
D000679:Amygdala / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000187:drug effects; D013779:Tetrodotoxin / Q000494:pharmacology; D014635:Valproic Acid / Q000494:pharmacology*
D013779:Tetrodotoxin; D014635:Valproic Acid; D001640:Bicuculline