NaVkanavat

NaVkanavat, also known as voltage-gated sodium channels, are a family of transmembrane proteins that mediate the fast sodium current underlying action potentials in neurons, muscle, and other excitable cells. They are essential for the initiation and propagation of electrical signals in the nervous system and heart.

The functional channel is formed primarily by a central alpha subunit, which consists of four homologous domains (I–IV), each with six transmembrane segments (S1–S6). The S4 segments act as voltage sensors, and rapid inactivation is controlled by the intracellular III–IV linker. Auxiliary beta subunits associate with the alpha subunit to modulate gating, kinetics, and cell-surface expression.

In humans, NaV channels are encoded by the SCN gene family, including SCN1A, SCN2A, SCN3A, SCN8A, SCN9A, SCN5A, and others. There is tissue-specific distribution among isoforms, with neuronal channels (for example NaV1.1–NaV1.9) and a cardiac isoform (NaV1.5) among the best characterized. Different isoforms exhibit distinct activation and inactivation properties that tailor electrical excitability to cellular context.

Functionally, NaV channels open in response to membrane depolarization, allowing a rapid influx of Na+ that drives the rising phase of the action potential; they then inactivate to terminate the current. They are targets for a range of drugs, including local anesthetics and antiarrhythmics. Tetrodotoxin blocks many NaV channels, though some isoforms (TTX-resistant) are less sensitive.

Mutations in NaV channels underlie various channelopathies, such as epilepsy (notably SCN1A), pain disorders linked to SCN9A, and cardiac arrhythmias associated with SCN5A.