Topiramate attenuates voltage-gated sodium currents in rat cerebellar granule cells

Abstract

Whole-cell, voltage-clamp recordings were made from rat cerebellar granule cells in culture under experimental conditions designed to study voltage-gated Na⁺ currents that were elicited by depolarizing commands from a holding potential of −60 mV up to +20 mV. These tetrodotoxin-sensitive inward currents were reduced in a dose-related manner by bath application of the structurally novel, anticonvulsant drug topiramate (10–1000 μM; n=16). Dose-response analysis of this effect revealed an IC₅₀ of 48.9 μM. Topiramate also made the steady-state inactivation 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 effects may contribute to control the sustained depolarizations with repetitive firing of action potentials that occur within neuronal networks during seizure activity. Therefore they may represent a mechanism of action for this novel anticonvulsant drug.