Neocortical potassium currents are enhanced by the antiepileptic drug lamotrigine

Cristina Zona, Virginia Tancredi, Patrizia Longone, Giovanna D'Arcangelo, Margherita D'Antuono, Mario Manfredi, Massimo Avoli

Research output: Contribution to journalArticle

Abstract

Purpose: We used field-potential recordings in slices of rat cerebral cortex along with whole-cell patch recordings from rat neocortical cells in culture to test the hypothesis that the antiepileptic drug (AED) lamotrigine (LTG) modulates K+-mediated, hyperpolarizing currents. Methods: Extracellular field-potential recordings were performed in neocortical slices obtained from Wistar rats aged 25-50 days. Rat neocortical neurons in culture were subjected to the whole-cell mode of voltage clamping under experimental conditions designed to study voltage-gated K+ currents. Results: In the in vitro slice preparation, LTG (100-400 μM) reduced and/or abolished epileptiform discharges induced by 4-aminopyridine (4AP, 100 μM; n = 10), at doses that were significantly higher than those required to affect epileptiform activity recorded in Mg2+-free medium (n = 8). We also discovered that in cultured cortical cells, LTG (100-500 μM; n = 13) increased a transient, 4AP-sensitive, outward current elicited by depolarizing commands in medium containing voltagegated Ca2+ and Na+ channel antagonists. Moreover, we did not observe any change in a late, tetraethylammonium-sensitive outward current. Conclusions: Our data indicate that LTG, in addition to the well-known reduction of voltage-gated Na+ currents, potentiates 4AP-sensitive, K+-mediated hyperpolarizing conductances in cortical neurons. This mechanism of action contributes to the anticonvulsant effects exerted by LTG in experimental models of epileptiform discharge, and presumably in clinical practice.

Original languageEnglish
Pages (from-to)685-690
Number of pages6
JournalEpilepsia
Volume43
Issue number7
DOIs
Publication statusPublished - 2002

Keywords

  • 4-Aminopyridine
  • Cortical cells
  • Epileptiform discharges
  • K currents
  • Lamotrigine

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

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