Carbamazepine and topiramate modulation of transient and persistent sodium currents studied in HEK293 cells expressing the Nav1.3 α-subunit

Abstract

Purpose: The transient and the persistent Na+ current play a distinct role in neuronal excitability. Several antiepileptic drugs (AEDs) modulate the transient Na+ current and block the persistent Na + current; both effects contribute to their antiepileptic properties. The interactions of the AEDs carbamazepine (CBZ) and topiramate (TPM) with the persistent and transient Na+ current were investigated. Methods: HEK293 cells stably expressing the α-subunit of the Na+ channel NaV1.3 were used to record Na+ currents under voltage-clamp by using the patch-clamp technique in whole-cell configuration and to investigate the effects of CBZ and TPM. Results: The persistent Na + current was present in all cells and constituted 10.3 ± 3.8% of the total current. CBZ partially blocked the persistent Na+ current in a concentration-dependent manner [median effective concentration (EC50), 16 ± 4 μM]. CBZ also shifted the steady-state inactivation of the transient Na+ current to negative potentials (EC50, 14 ± 11 μM). TPM partially blocked the persistent Na+ current with a much higher affinity (EC50, 61 ± 37 nM) than it affected the steady-state inactivation of the transient Na + current (EC50, 3.2 ± 1.8 μM). For the latter effect, TPM was at most half as effective as CBZ. Conclusions: The persistent Na+ current flowing through the α-subunit of the Na V1.3 channel is partially blocked by CBZ at about the same therapeutic concentrations at which it modulates the transient Na+ current, adding a distinct aspect to its anticonvulsant profile. The TPM-induced partial block of the persistent Na+ current, already effective at low concentrations, could be the dominant action of this drug on the Na + current. © 2007 International League Against Epilepsy.