Inhibition of the rat brain sodium channel Nav1.2 after prolonged exposure to gabapentin

Epilepsy Res. 2006 Aug;70(2-3):263-8. doi: 10.1016/j.eplepsyres.2006.03.007. Epub 2006 Apr 18.


Prolonged exposure of neurons to gabapentin inhibits repetitive firing of Na(+)-dependent action potentials. Here, we studied the effect of such prolonged exposure to gabapentin on a rat sodium channel, Nav1.2. After 3 days of continuous incubation with gabapentin (10-1000 microM), Nav1.2 current density was decreased dose-dependently relative to untreated cells. The reduction was 57% at 30 microM gabapentin, while higher concentrations (100-1000 microM) did not result in greater effects. Prolonged treatment with gabapentin also caused the channel to inactivate at more hyperpolarized potentials. These effects provide a mechanistic basis for the inhibition of Na(+)-dependent repetitive firing upon prolonged exposure to gabapentin and may contribute to its anticonvulsant activity.

MeSH terms

  • Action Potentials / drug effects
  • Amines / pharmacology*
  • Animals
  • Anticonvulsants / pharmacology*
  • Brain / drug effects*
  • Brain / physiology
  • Cell Line
  • Cricetinae
  • Cricetulus
  • Cyclohexanecarboxylic Acids / pharmacology*
  • Dose-Response Relationship, Drug
  • Gabapentin
  • NAV1.2 Voltage-Gated Sodium Channel
  • Nerve Tissue Proteins / drug effects*
  • Nerve Tissue Proteins / physiology
  • Patch-Clamp Techniques
  • Rats
  • Sodium Channels / drug effects*
  • Sodium Channels / physiology
  • gamma-Aminobutyric Acid / pharmacology*


  • Amines
  • Anticonvulsants
  • Cyclohexanecarboxylic Acids
  • NAV1.2 Voltage-Gated Sodium Channel
  • Nerve Tissue Proteins
  • Scn2A protein, rat
  • Sodium Channels
  • gamma-Aminobutyric Acid
  • Gabapentin