SCN9ANav17

SCN9ANav17 is the voltage-gated sodium channel Nav1.7, encoded by the human SCN9A gene. It functions as the pore-forming alpha subunit of a sodium-selective channel that contributes to the initiation and propagation of action potentials in peripheral sensory neurons, particularly nociceptors, and in some sympathetic neurons.

Nav1.7 is a single polypeptide consisting of four homologous domains (I–IV), each with six transmembrane segments. The S4 segments act as voltage sensors, and the pore-forming loop between domains forms the ion-conducting pathway. The channel opens in response to membrane depolarization and inactivates rapidly, and it is characterized as tetrodotoxin-sensitive in humans.

SCN9A is located on chromosome 2q24.3. Expression is highest in dorsal root ganglia and sympathetic ganglia, with additional expression in various peripheral nerves. Nav1.7 contributes to setting the threshold for action potential firing and to the amplification of small depolarizations that convey noxious stimuli.

Mutations in SCN9A cause notable human pain disorders. Gain-of-function mutations produce conditions such as inherited erythromelalgia and paroxysmal extreme pain disorder, with severe episodic or continuous pain. Loss-of-function mutations can cause congenital insensitivity to pain. These clinical associations highlight Nav1.7 as a major target for analgesic research.

Pharmacological interest centers on developing selective Nav1.7 inhibitors to reduce pain signaling while minimizing effects on other channels. Research uses human genetics, mouse models, and cellular systems to understand channel regulation, gating, and drug responsiveness.