KAVA EXTRACT INGREDIENTS, (-METHYSTICIN AND (+())-)-KAVAIN INHIBIT VOLTAGE-OPERATED NA+-CHANNELS IN RAT CA1 HIPPOCAMPAL-NEURONS/

The action of synthetic kava pyrones, (+)-methysticin and (+/-)-kavain , on voltage-operated Na+-channels was studied in whole-cell patch-cla mped CA1 hippocampal neurons. In doses of 1-400 mu M, both compounds e xerted a rapid and reversible inhibition of the peak amplitude of Na+- currents. Shifting holding membrane potential (V-hold), to more positi ve values enhanced their blocking effect. The drugs studied did not de monstrate use-dependent properties at 10 Hz stimulation but shifted h( infinity), curve toward more negative potentials, accelerated time-cou rse of inactivation and slowed down the recovery from inactivation. Vo ltage-dependence of Na+-channel inhibition can be explained by interac tion of (+)-methysticin and (+/-)-kavain with resting closed and inact ivated states of Na+-channel. (C) 1997 IBRO. Published by Elsevier Sci ence Ltd.