Inhibitory effect of lamotrigine on A-type potassium current in hippocampal neuron-derived H19-7 cells

Chin Wei Huang, Chao Ching Huang, Yen Chin Liu, Sheng Nan Wu

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Purpose: We investigated the effects of lamotrigine (LTG) on the rapidly inactivating A-type K+ current (IA) in embryonal hippocampal neurons. Methods: The whole-cell configuration of the patch-clamp technique was applied to investigate the ion currents in cultured hippocampal neuron-derived H19-7 cells in the presence of LTG. Effects of various related compounds on IA in H19-7 cells were compared. Results: LTG (30 μM-3 mM) caused a reversible reduction in the amplitude of IA. The median inhibitory concentration (IC50) value required for the inhibition of IA by LTG was 160 μM. 4-Aminopyridine (1 mM), quinidine (30 μM), and capsaicin (30 μM) were effective in suppressing the amplitude of IA, whereas tetraethylammonium chloride (1 mM) and gabapentin (100 μM) had no effect on it. The time course for the inactivation of IA was changed to the biexponential process during cell exposure to LTG (100 μM). LTG (300 μM) could shift the steady-state inactivation of IA to a more negative membrane potential by approximately - 10 mV, although it had no effect on the slope of the inactivation curve. Moreover, LTG (100 μM) produced a significant prolongation in the recovery of IA inactivation. Therefore in addition to the inhibition of voltage-dependent Na+ channels, LTG could interact with the A-type K+ channels to suppress the amplitude of IA. The blockade of I A by LTG does not simply reduce current magnitude, but alters current kinetics, suggesting a state-dependent blockade. LTG might have a higher affinity to the inactivated state than to the resting state of the IA channel. Conclusions: This study suggests that in hippocampal neurons, during exposure to LTG, the LTG-mediated inhibition of these K+ channels could be one of the ionic mechanisms underlying the increased neuronal excitability.

Original languageEnglish
Pages (from-to)729-736
Number of pages8
JournalEpilepsia
Volume45
Issue number7
DOIs
Publication statusPublished - Jul 2004
Externally publishedYes

Keywords

  • A-type K current
  • Hippocampal neurons
  • Lamotrigine

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

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