VALPROATE SELECTIVELY REDUCES THE PERSISTENT FRACTION OF NA+ CURRENT IN NEOCORTICAL NEURONS

The effect of valproate (VPA) on Na+ currents (INa), was studied by me ans of voltage clamp recordings using whole-cell patch clamp configura tion in 21 acutely dissociated neocortical neurons. Concentrations of VPA up to 200 mu M failed to induce any detectable decrease in fast IN a (I-Naf) but the persistent fraction (I-NaP) was significantly reduce d by low VPA concentrations (10-30 mu M), corresponding to the lower v alues of the 'therapeutic' range in epileptic patients. Since it is kn own that I-NaP critically regulates the firing properties of pyramidal neurons, it is suggested that the anticonvulsant effectiveness of VPA is mainly due to its effect on I-NaP. (C) 1998 Elsevier Science B.V. All rights reserved.