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 language | English |
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Pages (from-to) | 123-126 |
Number of pages | 4 |
Journal | Neuroscience Letters |
Volume | 231 |
Issue number | 3 |
DOIs | |
Publication status | Published - Aug 15 1997 |
Keywords
- Anticonvulsant drug
- Cerebellum
- Excitability
- Na currents
- Rat
- Topiramate
ASJC Scopus subject areas
- Neuroscience(all)