Sodium channel protein type 8 subunit alpha (Nav1.6) and Sodium channel protein type 10 subunit alpha (Nav1.8) (Nav1.6 and Nav1.8)

Voltage-gated sodium channels Nav1.6 and Nav1.8 are essential transmembrane proteins that mediate the rapid influx of sodium ions required for action potential initiation and propagation. Nav1.6, encoded by the SCN8A gene, is the primary sodium channel at the nodes of Ranvier in both the central and peripheral nervous systems, playing a vital role in repetitive neuronal firing and signal conduction speed (Wikipedia, 2024; MedlinePlus, 2017). Nav1.8, encoded by the SCN10A gene, is predominantly expressed in peripheral nociceptive neurons and is a key driver of pain signaling, particularly under inflammatory or neuropathic conditions (GeneCards, 2024; PMC, 2024). While Nav1.6 is a major therapeutic target for treating SCN8A-related epilepsies and neurodevelopmental disorders, Nav1.8 has emerged as a highly validated target for non-opioid pain management (PMC, 2023; NEJM, 2023). Selective inhibitors such as suzetrigine (VX-548) target Nav1.8 to provide analgesia without central nervous system side effects or addictive potential (Vertex, 2025; ResearchGate, 2025). Conversely, Nav1.6 inhibitors like relutrigine are being developed to reduce neuronal hyperexcitability in seizure disorders (MedChemExpress, 2024). Together, these channels are fundamental to the physiological regulation of sensory and motor pathways, and their dysfunction is linked to a wide range of neurological and pain-related pathologies.

Other names

SCN8ASCN10APN4PN3SNSSodium channel protein type VIII alphaSodium channel protein type X alphaVoltage-gated sodium channel type VIII alphaVoltage-gated sodium channel type X alpha

Voltage-gated sodium channel inhibition; Suzetrigine acts as an allosteric inhibitor by binding to the second voltage-sensing domain (VSD2) to stabilize the closed state of the channel.