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Voltage-gated sodium channels (NaV) are essential for the generation of action potentials and for cell excitability. NaV channels are activated in response to depolarization and selectively allow flow of Na+ ions. To date, nine NaV alpha subunits have been cloned and named NaV1.1-NaV1.9. The NaV channels are classified into two groups according to their sensitivity to tetrodotoxin (TTX): TTX-sensitive (NaV1.1, NaV1.2, NaV1.3, NaV1.4, NaV1.6 and NaV1.7) and TTX-resistant (NaV1.5, NaV1.8 and NaV1.9). Mammalian sodium channels are heterotrimers, composed of a central, pore-forming alpha subunit and two auxiliary beta subunits. The expression of the alpha subunit isoform is developmentally regulated and tissue specific. Sodium channels in the adult central nervous system and heart contain beta 1 through beta 4 subunits, whereas sodium channels in adult skeletal muscle have only the beta 1 subunit.
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