Sodium channel protein type 8 subunit alpha (NaV1.6) (NaV1.6)

Sodium channel protein type 8 subunit alpha (NaV1.6) is a voltage-gated sodium channel encoded by the SCN8A gene, primarily localized at the axon initial segment and nodes of Ranvier in the central and peripheral nervous systems (UniProt: Q9UQD0). It plays a fundamental role in the initiation and saltatory conduction of action potentials, contributing significantly to both peak and persistent sodium currents that regulate neuronal firing rates (PubMed: 28823310). Mutations in the SCN8A gene are linked to a spectrum of neurological disorders, most notably developmental and epileptic encephalopathy type 13 (DEE13), where gain-of-function mutations lead to neuronal hyperexcitability (NCBI Gene: 6334). Beyond epilepsy, NaV1.6 is implicated in the maintenance of chronic and neuropathic pain states due to its role in sensory neuron excitability (PubMed: 31433458). While traditional anticonvulsants like carbamazepine and phenytoin inhibit NaV1.6 non-selectively, modern drug discovery focuses on isoform-selective inhibitors such as NBI-921352 and XEN901 to minimize off-target effects on cardiac (NaV1.5) or other neuronal (NaV1.1) channels (ClinicalTrials.gov). These selective therapies aim to provide more precise control over seizure activity and pain while reducing the risk of ataxia and cardiac toxicity associated with broad-spectrum sodium channel blockade.

Other names

SCN8ASodium channel voltage-gated type VIII alpha subunitCerIIIPN4Voltage-gated sodium channel subunit alpha Nav1.6

Sodium channel blocker