Sodium channel protein type 3 subunit alpha (SCN3A) (NaV1.3)

Sodium channel protein type 3 subunit alpha (NaV1.3) is a voltage-gated sodium channel primarily responsible for the generation and propagation of action potentials in the developing central nervous system (UniProt P35498). While its expression typically declines after birth in most tissues, NaV1.3 is notably upregulated in adult peripheral sensory neurons following nerve injury, contributing significantly to the hyperexcitability associated with chronic neuropathic pain (PubMed PMID: 11739595). Mutations in the SCN3A gene, which encodes this channel, are also linked to various forms of pediatric epilepsy and malformations of cortical development (PubMed PMID: 30531925). Pharmacologically, NaV1.3 is a target for various anticonvulsants and local anesthetics, although many current clinical agents lack the isoform selectivity needed to avoid side effects from other sodium channel variants. Research continues to focus on developing isoform-specific inhibitors to treat chronic pain and seizure disorders with improved safety profiles (IUPHAR/BPS Guide to Pharmacology). As a pore-forming subunit, it mediates the voltage-dependent sodium permeability of excitable membranes, making it a critical component of neuronal signaling pathways.

Other names

SCN3ASodium channel protein type III subunit alphaVoltage-gated sodium channel type III alpha subunitNAC3Nav1.3

Blockade of the pore-forming alpha subunit to inhibit sodium ion influx and stabilization of the inactivated state of the channel, thereby reducing the frequency of neuronal action potential firing (IUPHAR/BPS Guide to Pharmacology).