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 mu M), Nav1.2 current density was decreased dose-dependently relative to untreated cells. The reduction was 57% at 30 mu M gabapentin, while higher concentrations (100-1000 mu M) 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. (c) 2006 Elsevier B.V. All rights reserved.