Lamotrigine reduces voltage-gated sodium currents in rat central neurons in culture

Cristina Zona, Massimo Avoli

Research output: Contribution to journalArticle

Abstract

Purpose: To study the mechanism or mechanisms of action of lamotrigine (LTG) and, in particular, to establish its effects on the function of NA+ channels in mammalian central neurons. Methods: Rat cerebellar granule cells in culture were subjected to the whole-cell mode of voltage clamping under experimental conditions designed to study voltage-gated Na+ currents. Results: Extracellular application of LTG (10-500 μM, n = 21) decreased in a dose-related manner a tetrodotoxin-sensitive inward current that was elicited by depolarizing commands (from -80 to + 20mV). The peak amplitude of this Na+-mediated current was diminished by 38.8 ± 12.2% (mean ± SD, n = 6) during application of 100 μM LTG, and the dose-response curve of this effect indicated an IC50 of 145 μM. The reduction in the inward currents produced by LTG was not associate with any signficant change in the current decay, whereas the voltage dependency of the steady-state inactivation shifted toward more negative values (midpoint of the inactivation curve: -47.5 and - 59.0 mV under control conditions and during application of 100 μM LTG, respectively, n = 4). Conclusions: Our findings indicate that LTG reduces the amplitude of voltage-gated Na+ inward current in rat cerebellar granule cells and induces a negative shift of the steady-state inactivation curve. Both mechanisms may he instrumental in controlling the repetitive tiring of action potentials (AP) that occurs in neuronal networks during seizure activity.

Original languageEnglish
Pages (from-to)522-525
Number of pages4
JournalEpilepsia
Volume38
Issue number5
Publication statusPublished - 1997

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Sodium
Neurons
Tetrodotoxin
Constriction
Action Potentials
Inhibitory Concentration 50
lamotrigine
Seizures
Cell Culture Techniques

Keywords

  • Antiepileptic drugs
  • Granule cells
  • Lamotrigine
  • Rat
  • Sodium currents

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

Cite this

Lamotrigine reduces voltage-gated sodium currents in rat central neurons in culture. / Zona, Cristina; Avoli, Massimo.

In: Epilepsia, Vol. 38, No. 5, 1997, p. 522-525.

Research output: Contribution to journalArticle

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AU - Avoli, Massimo

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