Valproate reduces excitability by blockage of sodium and potassium conductance

Effects of the antiepileptic drug valproate on sodium and potassium currents in the nodal membrane of peripheral nerve fibers of Xenopus laevis were determined by voltage- and current-clamp experiments. Under voltage-clamp conditions, a reduction of both sodium and potassium conductance (in a ratio of 2:1) was observed. Typically, 2.4 mM (400 mg/L) valproate reduced the sodium current 54% and the potassium current 26%, at a membrane potential of 5 mV. Valproate did not affect the leakage conductance. The reduction of potassium conductance was voltage dependent, being more pronounced at more positive membrane potentials. For the sodium system, a voltage dependency of the blockage could not be established. Under current-clamp conditions, valproate caused a reduction of excitability of nerve membrane: amplitude of the action potential and maximum rate of rise were decreased, whereas threshold potential was increased. The ability to follow high-frequency stimulation was impaired.