Sodium channel protein type 5 subunit alpha (SCN5A) and Sodium channel protein type 9 subunit alpha (SCN9A) (NaV1.5; NaV1.7)

Voltage-gated sodium channels (NaVs) are transmembrane proteins that facilitate the rapid influx of sodium ions, essential for the initiation and propagation of action potentials in excitable tissues (StatPearls: NBK541024). This target group primarily includes NaV1.5 (Sodium channel protein type 5 subunit alpha) and NaV1.7 (Sodium channel protein type 9 subunit alpha). NaV1.5 is the principal sodium channel in the heart, where it governs cardiac rhythm and conduction; mutations in the SCN5A gene are associated with life-threatening arrhythmias such as Brugada syndrome and Long QT syndrome type 3 (UniProt: P35498; PubMed: 11910022). NaV1.7 is highly expressed in peripheral sensory neurons and plays a pivotal role in nociception by setting the threshold for pain signaling (PubMed: 23400565). Gain-of-function mutations in SCN9A (NaV1.7) cause severe pain disorders like erythromelalgia, while loss-of-function mutations result in congenital insensitivity to pain (UniProt: Q15858). Clinically, NaV1.5 is targeted by Class I antiarrhythmic agents like mexiletine and flecainide to treat ventricular arrhythmias (StatPearls: NBK532944). NaV1.7 is a major focus for the development of selective, non-opioid analgesics to treat chronic and neuropathic pain, though achieving sufficient selectivity over other NaV isoforms remains a significant therapeutic challenge (Nature Reviews Drug Discovery: 10.1038/nrd.2017.207). Overall, these channels are critical therapeutic targets for cardiovascular and neurological conditions.

Other names

SCN5ASCN9ANaV1.5NaV1.7Sodium channel protein type 5 subunit alphaSodium channel protein type 9 subunit alphaVGSCCardiac sodium channelPN1

Inhibition of sodium ion conductance by binding to the alpha subunit pore or modulating gating transitions to stabilize the non-conducting inactivated state.