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

Epilepsia
C Zona, M Avoli

Abstract

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. 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. Extracellular application of LTG (10-500 microM, n = 21) decreased in a dose-related manner a tetrodotoxin-sensitive inward current that was elicited by depolarizing commands (from -80 to +20 mV). The peak amplitude of this Na(+)-mediated current was diminished by 38.8 +/- 12.2% (mean +/- SD, n = 6) during application of 100 microM LTG, and the dose-response curve of this effect indicated an IC50 of 145 microM. The reduction in the inward currents produced by LTG was not associate with any significant 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 microM LTG, respectively, n = 4). Our findings indicate that LTG reduces the amplitude of voltage-gated Na+ inward current in rat cerebellar granule ce...Continue Reading

References

Dec 1, 1982·Journal of Neurophysiology·B W ConnorsD A Prince
Sep 1, 1993·Journal of Neurophysiology·D MattiaM Avoli

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Citations

Jul 13, 2001·Pharmacology & Therapeutics·P KwanM J Brodie
May 26, 1998·Brain Research. Brain Research Reviews·D S Ragsdale, M Avoli
Sep 9, 2011·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Xiaohua LiRichard C Shelton
Nov 9, 2002·Epilepsia·Rüdiger Köhling
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Jul 7, 2001·Epilepsia·M AvoliG Avanzini
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Feb 13, 2020·Focus : Journal of Life Long Learning in Psychiatry·Joseph F Goldberg
Jan 2, 2021·Epilepsy Research·Yang ZengWei-Ping Liao

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