Voltage-gated sodium channel (also referred to as Nav channel family members) (VGSC or Nav)

Voltage-gated sodium channels are transmembrane ion channels essential for initiating and propagating action potentials in nerve and muscle cells.[1][5] In peripheral nerves, these channels are key determinants of sensory neuron excitability, integrating generator potentials and initiating action potentials that transmit pain and other sensory information to the central nervous system.[2] The channel consists of a pore-forming alpha subunit composed of four homologous domains with voltage-sensing regions (S1-S4 segments) and a central ion-conducting pore (S5-S6 segments), along with auxiliary beta subunits that modulate gating kinetics and channel localization.[4][6] Specific peripheral nerve isoforms including Nav1.7, Nav1.8, and Nav1.9 play critical roles in pain signaling, with mutations in these channels associated with chronic pain syndromes, erythromelalgia, and channelopathy-associated pain insensitivity.[1][4][7] Voltage-gated sodium channels are validated therapeutic targets, with drugs acting as gating modifiers or pore blockers to alter channel function for pain management and treatment of other neurological conditions.[5] The tissue-specific expression of different channel isoforms and their distinct kinetic properties provide opportunities for selective therapeutic intervention while minimizing off-target effects on cardiac and skeletal muscle sodium channels.

Other names

Voltage-gated sodium channel alpha subunitNa channelSodium channelNav1.1 through Nav1.9 (specific isoforms)SCN1A-SCN5A, SCN8A-SCN11A (gene names for different isoforms)

Drugs targeting voltage-gated sodium channels act as gating modifiers, altering voltage-dependent gating properties; pore blockers, physically occluding the ion channel pore; fast inactivation modifiers, affecting rapid decay of sodium current; or voltage sensor modulators, altering S4 segment function and channel opening kinetics.