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

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.