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

Cristina Zona, Maria Teresa Ciotti, Massimo Avoli

Research output: Contribution to journalArticlepeer-review

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 (10-1000μM; 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.

Original languageEnglish
Pages (from-to)123-126
Number of pages4
JournalNeuroscience Letters
Volume231
Issue number3
DOIs
Publication statusPublished - Aug 15 1997

Keywords

  • Anticonvulsant drug
  • Cerebellum
  • Excitability
  • Na currents
  • Rat
  • Topiramate

ASJC Scopus subject areas

  • Neuroscience(all)

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