Na_v1.6

Naᵥ1.6, encoded by SCN8A, is a major neuronal voltage-gated sodium channel that supports action potential initiation and propagation in the nervous system^[1]. Mechanistically, Naᵥ1.6 contributes persistent and resurgent sodium currents, which sustain repetitive firing and shape neuronal excitability^[2][3]. Its ankyrinG-binding motif targets the channel to axon initial segments and nodes of Ranvier, linking channel localization to spike initiation and saltatory conduction^[4]. In disease models, SCN8A mutations associate with epileptic encephalopathy, intellectual disability, and altered persistent or resurgent current properties^[1][5]. Compared with related isoforms, human Naᵥ1.6 generates larger resurgent currents than human Naᵥ1.1, making isoform distinction important in sodium channel electrophysiology^[6]. For experimental applications, cannabidiol preferentially reduced resurgent and persistent currents from wild-type and epilepsy-associated mutant Naᵥ1.6 channels, supporting its use as a tool for studying aberrant Naᵥ1.6 activity^[7].