Inhibition of sodium current by carbamazepine in dorsal root ganglion neurons in vitro.

ABSTRACT

Carbamazepine (CBZ), one of the most commonly prescribed antiepileptic drug, is proposed to inhibit Na+ channel. In this study, we have investigated the effects of CBZ on Na+ current, evoked in cultured dorsal root ganglion (DRG) neurons from neonatal rats using whole cell patch clamp technique. In small DRG neurons (20–25 μm), Na+ current was obtained by blocking K+ and Ca2+ currents with appropriate ion replacement and channel blockers. Separation of the Na+ current components was achieved on the basis of response to the conditioning voltage. The CBZ depressed Na+ current in a dose-dependent manner. The maximal Na+ current was depressed at 300 μM of CBZ, where 94±5.1% of depression was observed. The depression of normalized current amplitude was found to be 72±13.2%, 84±10%, 85±7.1% and 95±5.2% at 10, 30, 100 and 300 μM of CBZ concentrations, respectively, at –20 mV test pulse, when compared with control. The depression of current amplitude was observed as 48±12.3%, 42±15.2%, 71±17.7% and 90±5.8% at 10, 30, 100 and 300 μM of CBZ concentration, respectively, at 0 mV voltage pulse. The depression of Na+ currents was found to be dose-dependant at –20 and –10 mV but not at 0 mV. It is concluded that the depression of Na+ currents by CBZ may be responsible for inhibiting the neurotransmitter release.