Voltage-gated sodium channel (NaV1.1–NaV1.9) (NaV1.1–NaV1.9)

Voltage-gated sodium channels (NaV1.1–NaV1.9) are a family of transmembrane proteins essential for the initiation and propagation of action potentials in excitable cells, including neurons, cardiomyocytes, and skeletal muscle fibers [14, 17]. These channels open in response to membrane depolarization, allowing the rapid influx of sodium ions into the cell [21]. The family consists of nine alpha-subunits (NaV1.1 to NaV1.9), each with distinct tissue distributions and physiological roles [3, 14]. For instance, NaV1.1, NaV1.2, and NaV1.6 are primarily found in the central nervous system, while NaV1.7, NaV1.8, and NaV1.9 are localized in the peripheral nervous system [16, 23]. Mutations in the genes encoding these channels are linked to a wide range of "channelopathies," such as epilepsy, chronic pain syndromes, and cardiac arrhythmias [17, 21]. Pharmacologically, these channels are the primary targets for local anesthetics, antiarrhythmics, and anticonvulsants [4, 12]. Most of these drugs work by blocking the pore or stabilizing the inactivated state of the channel to reduce hyperexcitability [4, 12]. Modern drug discovery focuses on developing subtype-selective inhibitors to minimize systemic side effects, particularly for treating pain and epilepsy [7, 9]. These channels are also the targets of various natural toxins, which have been instrumental in studying their structure and function [15, 17].

Other names

Voltage-gated sodium channel alpha subunitVGSCSodium channel protein type 1 subunit alphaSodium channel protein type 2 subunit alphaSodium channel protein type 3 subunit alphaSodium channel protein type 4 subunit alphaSodium channel protein type 5 subunit alphaSodium channel protein type 8 subunit alphaSodium channel protein type 9 subunit alphaSodium channel protein type 10 subunit alphaSodium channel protein type 11 subunit alphaSCN1ASCN2ASCN3ASCN4ASCN5ASCN8ASCN9ASCN10ASCN11A

Sodium channel blocker; stabilization of the inactivated state of the channel.