The Effect of Lamotrigine on Na_v1.4 Voltage-Gated Sodium Channels

Abstract

Lamotrigine (LTG) is an anticonvulsant drug used in the treatment of epilepsy and bipolar disorder and it has been known that LTG targets voltage-dependent sodium channels (VGSCs). In this study, we investigated the effect of LTG on the Na_v1.4 Na⁺ current using HEK293 cells expressing mouse Na_v1.4 VGSCs. By the treatment of LTG, Na_v1.4 Na⁺ current was inhibited in a dose-dependent manner. Moreover, 100 μM LTG decreased Na_v1.4 Na⁺ current around 40% and shifted the V_1/2 of the inactivation curve to the hyperpolarization side by 20.96 mV. These findings suggest that LTG inhibits Na_v1.4 Na⁺ current and modifies the kinetics of the inactivated state.