Voltage-gated sodium channel, neuronal subtype (Nav)

Voltage-gated sodium channels (Nav) are transmembrane proteins essential for the initiation and propagation of action potentials in neurons (Catterall, 2012, Journal of Physiology). The neuronal subtypes are categorized into those primarily in the central nervous system (Nav1.1, Nav1.2, Nav1.3, and Nav1.6) and those in the peripheral nervous system (Nav1.7, Nav1.8, and Nav1.9) (Dib-Hajj et al., 2013, Nature Reviews Neuroscience). These channels facilitate the rapid influx of sodium ions in response to membrane depolarization, a process vital for electrical signaling and neurotransmission. Mutations in the genes encoding these channels are linked to a spectrum of neurological disorders, including various forms of epilepsy and chronic pain conditions like inherited erythromelalgia (Meisler & Kearney, 2005, Journal of Clinical Investigation). Pharmacologically, these channels are targeted by anticonvulsants and local anesthetics that bind to the pore-forming alpha subunit to stabilize the inactivated state, thereby reducing neuronal hyperexcitability (StatPearls, 2023, Physiology, Sodium Channels). Current drug development efforts are focused on achieving subtype selectivity, particularly for Nav1.7 and Nav1.8, to provide effective analgesia without the central or cardiac side effects associated with non-selective sodium channel blockers (Baguet et al., 2020, Expert Opinion on Therapeutic Targets).

Other names

Voltage-gated sodium channel (VGSC)Sodium channel protein type 1 subunit alpha (Nav1.1)Sodium channel protein type 2 subunit alpha (Nav1.2)Sodium channel protein type 3 subunit alpha (Nav1.3)Sodium channel protein type 8 subunit alpha (Nav1.6)Sodium channel protein type 9 subunit alpha (Nav1.7)Sodium channel protein type 10 subunit alpha (Nav1.8)Sodium channel protein type 11 subunit alpha (Nav1.9)SCN1ASCN2ASCN3ASCN8ASCN9ASCN10ASCN11A

Inhibition of sodium ion influx by binding to the alpha-subunit, typically stabilizing the inactivated state of the channel to prevent repetitive firing (Catterall, 2012, Journal of Physiology; StatPearls, 2023).