Neuronal voltage-gated sodium channel (Nav) (Nav)

Neuronal voltage-gated sodium channels (Nav) are specialized transmembrane proteins that play a fundamental role in the electrical signaling of the nervous system by facilitating the rapid influx of sodium ions (StatPearls, 2023 [1]). This ion flux is the primary driver for the depolarization phase of action potentials in both the central and peripheral nervous systems (NCBI, 2022 [3]). The neuronal Nav family comprises several distinct alpha-subunit isoforms, including Nav1.1, Nav1.2, Nav1.3, and Nav1.6 in the brain, and Nav1.7, Nav1.8, and Nav1.9 in peripheral sensory neurons (UniProt, 2024 [2]). Genetic mutations in these channels are linked to a wide spectrum of neurological disorders known as channelopathies, ranging from severe myoclonic epilepsy of infancy to congenital insensitivity to pain (PubMed, 2021 [4]). Pharmacologically, these channels are the primary targets for a variety of drugs, including local anesthetics, anticonvulsants, and certain antiarrhythmics (PubChem, 2024 [5]). These therapeutic agents typically function by binding to the inner pore of the channel or stabilizing its inactivated state, thereby suppressing the neuronal hyperexcitability associated with seizures and chronic pain (NCBI, 2022 [3]).

Other names

Voltage-gated sodium channelVGSCSodium channel proteinNav1.xNeuronal sodium channel

Most clinically used drugs are pore blockers that exhibit state-dependent binding, specifically targeting the inactivated state of the channel to inhibit high-frequency neuronal firing while sparing normal activity (NCBI, 2022 [3]; StatPearls, 2023 [1]).