Sodium channel protein type 5 subunit alpha and Sodium channel protein type 9 subunit alpha (Nav1.5 and Nav1.7)

Voltage-gated sodium channels (Nav) are integral membrane proteins that facilitate the rapid influx of sodium ions, essential for the initiation and propagation of action potentials in excitable tissues. This specific target profile focuses on Nav1.5 (encoded by SCN5A) and Nav1.7 (encoded by SCN9A), which play distinct but critical roles in human physiology. Nav1.5 is the primary sodium channel in the heart, responsible for the rapid upstroke of the cardiac action potential and proper conduction (UniProt P35498). In contrast, Nav1.7 is predominantly expressed in the peripheral nervous system, particularly in dorsal root ganglion neurons, where it serves as a key regulator of pain signaling by amplifying sub-threshold stimuli (PubMed 23536227). While Nav1.7 is highly sensitive to tetrodotoxin (TTX), Nav1.5 is relatively TTX-resistant, a distinction that is crucial for pharmacological targeting (PubMed 10751124). Mutations in these channels are associated with severe disorders, including cardiac arrhythmias like Brugada syndrome for Nav1.5, and chronic pain syndromes or insensitivity to pain for Nav1.7 (Nature Reviews Drug Discovery, 2021). Therapeutic strategies involve small molecule inhibitors that aim to block the channel pore or stabilize inactivated states, though achieving high selectivity for Nav1.7 over Nav1.5 is vital to avoid life-threatening cardiotoxicity (Journal of Medicinal Chemistry, 2018).

Other names

SCN5ASCN9AVoltage-gated sodium channel alpha subunit 5Voltage-gated sodium channel alpha subunit 9VGSCPN1SkM2H1Nav1.5Nav1.7

Inhibition of sodium ion influx through the channel pore or stabilization of the inactivated state to prevent repetitive firing and reduce cellular excitability.