Sodium channel protein type 5 subunit alpha (Na_v1.5), Sodium channel protein type 9 subunit alpha (Na_v1.7), and Sodium channel protein type 10 subunit alpha (Na_v1.8) (Na_v1.5/1.7/1.8)

Voltage-gated sodium channels (Na_v) are transmembrane proteins that facilitate the rapid influx of sodium ions, a process essential for the initiation and propagation of action potentials in excitable tissues [IUPHAR/BPS Guide to Pharmacology]. This target profile encompasses three distinct alpha subunits: Na_v1.5 (SCN5A), Na_v1.7 (SCN9A), and Na_v1.8 (SCN10A). Na_v1.5 is the primary sodium channel in the heart, where it governs cardiac conduction; mutations in SCN5A are linked to life-threatening arrhythmias such as Brugada syndrome and Long QT syndrome type 3 [UniProt P35498]. Na_v1.7 and Na_v1.8 are predominantly expressed in the peripheral nervous system and are critical mediators of pain signaling (nociception), with Na_v1.7 acting as a threshold setter and Na_v1.8 contributing to the action potential upstroke in nociceptors [UniProt Q15858, Q9Y5Y9]. While traditional sodium channel blockers like lidocaine are non-selective and carry risks of cardiotoxicity and central nervous system side effects, modern drug discovery focuses on isoform-selective inhibitors, such as the Na_v1.8-selective agent suzetrigine (VX-548), to provide targeted analgesia [Vertex Pharmaceuticals, 2024; Nature Reviews Neuroscience, 2013].

Other names

SCN5ASCN9ASCN10AVoltage-gated sodium channelVGSCTetrodotoxin-resistant sodium channelPeripheral nerve sodium channelPN1PN3

Inhibition of sodium ion influx through the channel pore or stabilization of the inactivated state of the channel to prevent action potential propagation.