RILUZOLE INTERACTS WITH VOLTAGE-ACTIVATED SODIUM AND POTASSIUM CURRENTS IN CULTURED RAT CORTICAL-NEURONS

The actions of the neuroprotective and anticonvulsant agent riluzole o n voltage-activated currents were studied in primary cultures of rat c ortical neurons by using whole-cell patch-clamp recording techniques. Isolated Na+, Ca2+ and K+ currents were generated in these cells by de polarizing commands from a holding potential of -80 mV. Riluzole (10-3 00 mu M) reversibly reduced in a dose-dependent manner the inward Nacurrents with an IC50 of 51 mu M in all the tested neurons (n=29). Thi s drug also shifted the steady-state inactivation curve of the sodium current towards more negative values (abour 20 mV, n=15) while it did not change significantly the decay phase of the Na+ current. Furthermo re, riluzole (100 and 300 mu M; n=5 and n=3, respectively) did not mod ulate the inward Ca2+ currents evoked by depolarizing steps on cortica l cells. An additional concentration-dependent effect of riluzole was observed on the outward potassium currents. In fact, while the amplitu de of the peak of the outward current (I-A) was not changed significan tly, the amplitude of the late component of the outward K+ current (Is s) was markedly decreased during the perfusion of riluzole (IC50=88 mu M; n=16). It is concluded that riluzole modulates the Na+- and the la te K+-dependent currents in cortical neurons. Both phenomena may expla in, at least in part, the anticonvulsant and neuroprotective propertie s of this compound. (C) 1998 IBRO. Published by Elsevier Science Ltd.