Voltage-gated sodium channel (also referred to as Nav channel) (Nav (or VGSC for voltage-gated sodium channel))

Voltage-gated sodium channels (Nav channels) are integral membrane proteins that form ion-conducting pores responsible for initiating and propagating action potentials in neurons and muscle cells[1][11]. These channels consist of a pore-forming alpha subunit composed of four homologous domains, each containing six transmembrane segments, along with one to two regulatory beta subunits[1][7]. The channel's voltage sensitivity arises from positively charged amino acids in the S4 segment, which acts as a voltage sensor and undergoes conformational changes to open the pore upon membrane depolarization[7]. Nine distinct sodium channel subtypes (Nav1.1 through Nav1.9) are expressed in different tissues with specialized functions[7]. Nav1.7, Nav1.8, and Nav1.9 are preferentially expressed in nociceptors (pain-sensing neurons) and play critical roles in pain signal transmission, making them attractive therapeutic targets[2][4]. Nav1.8, which is expressed exclusively in peripheral sensory neurons rather than the central nervous system, represents a particularly promising target for pain treatment because inhibition can relieve pain without the risk of motor dysfunction or CNS-related side effects associated with non-selective blockers[4]. Genetic evidence validates Nav1.7 as a therapeutic target: gain-of-function mutations cause erythromelalgia (increased pain), while loss-of-function mutations result in congenital insensitivity to pain with otherwise normal neurological function[2]. Current drug development efforts focus on creating subtype-specific sodium channel blockers to maximize analgesic efficacy while minimizing unwanted side effects[2][4].

Other names

Voltage-gated sodium channelVGSCNav channelNeuronal sodium channelVoltage-sensitive sodium channel

Channel blockade/inhibition to reduce sodium ion influx. Reduction of action potential propagation. Selective subtype inhibition (Nav1.7, Nav1.8, Nav1.9 preferred for pain). TTX-sensitive vs. TTX-resistant channel targeting.