EFFECT OF VALPROIC ACID ON SODIUM CURRENTS IN CORTICAL-NEURONS FROM PATIENTS WITH PHARMACO-RESISTANT TEMPORAL-LOBE EPILEPSY

In a selected group of temporal lobe epilepsy patients with seizures r efractory to pharmacological treatment, pharmacological seizure contro l can be attained by surgical resection of the epileptic zone. We inve stigated to what extent pharmaco-resistance is reflected in a reduced response at the cellular level, in neurons acutely isolated from the t emporal cortex resected in 20 patients. We studied the effect of valpr oic acid (VPA) on the transient sodium current, measured under whole-c ell voltage-clamp conditions. We compared neurons from patients with t emporal lobe sclerosis (S) with neurons from patients without hippocam pal sclerosis (nS) and compared hippocampal CA1 neurons (CA) with neoc ortical neurons CNC). We could not detect differences in the voltage d ependence and kinetics of sodium current activation and inactivation i n any of the group comparisons. VPA shifted the voltage dependence of steady-state inactivation (expressed as V-h,V-i in a Boltzmann fit) to more hyperpolarized levels. The shift induced by 2 mM VPA was - 5.1 /- 0.7 mV in CA-S (n = 13), - 5.1 +/- 0.7 mV in CA-nS (n = 25), - 4.3 +/- 0.5 mV in NC-S (n = 17) and - 4.9 +/- 0.5 mV in NC-nS (n = 16) The relation between concentration and voltage shift had an EC50 of 1.4 /- 0.2 mM VPA (n = 16) and a maximal shift of 9.6 +/- 0.9 mV. We concl ude that pharmaco-resistance in these patients is not associated with a changed modulation of the sodium current by VPA. Results are discuss ed in the light of a reduced sodium current modulation by carbamazepin e in CA1 neurons of patients with hippocampal sclerosis and of similar observations in the kindling model of epileptogenesis. (C) 1998 Elsev ier Science B.V. All rights reserved.