A family of multisubunit ion channels with an aqueous pore ~0.4 nm diameter formed by the α subunits, with a negatively charged interior that inhibits the passage of anions. The various β subunits confer different responsiveness on channels, according to the tissue. The channel is responsible for electrical excitability of neurons, and a small depolarization of the cell (usually caused by an approaching action potential), triggers the channel to open. Within a millisecond ~1000 sodium ions pass through before the channel spontaneously closes. The channel is then refractory until the membrane potential approaches the resting potential. There are around 100 channels/μm2 in unmyelinated axons, but in myelinated axons they are concentrated at the nodes of Ranvier. Mutations in either the α or β subunits of the neuronal NaV1.1 (SCN1A and B) cause various forms of epilepsy. NaV1.2 (SCN2A) is similar to NaV1.1 but found in caudal regions of the brain; mutations cause febrile seizures. NaV1.3 is also found in the central nervous system. NaV1.4 (SCN4A and -B) is the skeletal muscle form and mutations in the gene are involved in various muscular disorders, including hyperkalemic periodic paralysis, myotonia, and hypokalemic periodic paralysis; mutations in SCN4B cause long QT syndrome-10. NaV1.5 is expressed in the heart, brain, and gastrointestinal tract, and mutations in the gene SCN5A cause long QT syndrome-3 and Brugada syndrome-1. NaV1.6 (alpha subunit encoded by SCN8A) may be defective in hereditary neurodegenerative diseases. SCN7A (previously SCN6A) is thought to be the sodium-level sensor in the brain. Mutations in SCN9A (alpha subunit of NaV1.7), the major sodium channel expressed in bronchial and arterial smooth muscle, cause primary erythromelalgia, congenital insensitivity to pain, and paroxysmal extreme pain disorder. NaV1.8 (SCN10A) is specific to peripheral sensory neurons. NaV1.9 (SCN11A) mediates brain-derived neurotrophic factor-evoked membrane depolarization through the receptor tyrosine kinase NTRK2 and is implicated in inflammatory but not acute pain. Many toxins (see anthopleurins; batrachotoxins; brevetoxins; calitoxins; ciguatoxins; conotoxins; jingzhaotoxin-III; saxitoxin; scorpion toxins; tetrodotoxin; veratridine) affect the channel with serious consequences. Compare amiloride-sensitive sodium channels.
Subjects: Medicine and Health.