TOPIRAMATE ATTENUATES VOLTAGE-GATED SODIUM CURRENTS IN RAT CEREBELLARGRANULE CELLS

Whole-cell, voltage-clamp recordings were made from rat cerebellar gra nule cells in culture under experimental conditions designed to study voltage-gated Nat currents that were elicited by depolarizing commands from a holding potential of -60 mV up to +20 mV. These tetrodotoxin-s ensitive inward currents were reduced in a dose-related manner by bath application of the structurally novel, anticonvulsant drug topiramate (10-1000 mu M; n = 16). Dose-response analysis of this effect reveale d an IC50 Of 48.9 mu M. Topiramate also made the steady-state inactiva tion curve of this current shift toward more negative values (midpoint of the inactivation curve -46.9 mV under control conditions and -56.5 mV during topiramate application; n = 5). We propose that these effec ts may contribute to control the sustained depolarizations with repeti tive firing of action potentials that occur within neuronal networks d uring seizure activity. Therefore they may represent a mechanism of ac tion for this novel anticonvulsant drug. (C) 1997 Elsevier Science Ire land Ltd.