Dual-pocket inhibition of Na_v channels by the antiepileptic drug lamotrigine.

ABSTRACT: Voltage-gated sodium (Na_v) channels govern membrane excitability, thus setting the foundation for various physiological and neuronal processes. Na_v channels serve as the primary targets for several classes of widely used and investigational drugs, including local anesthetics, antiepileptic drugs, antiarrhythmics, and analgesics. In this study, we present cryogenic electron microscopy (cryo-EM) structures of human Na_v1.7 bound to two clinical drugs, riluzole (RLZ) and lamotrigine (LTG), at resolutions of 2.9 Å and 2.7 Å, respectively. A 3D EM reconstruction of ligand-free Na_v1.7 was also obtained at 2.1 Å resolution. RLZ resides in the central cavity of the pore domain and is coordinated by residues from repeats III and IV. Whereas one LTG molecul

SUBMITTER: Huang J 

PROVIDER: S-EPMC10576118 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature