Voltage-gated sodium channels (Nav) are essential for the generation of action potentials and for cell excitability.1 Nav channels are activated in response to depolarization and selectively allow flow of Na+ ions. The Nav channels are classified into two groups according to their sensitivity to Tetrodotoxin (TTX): TTX-sensitive and TTX-resistant channels.2-3 Mammalian sodium channels are heterotrimers, composed of a central, pore-forming α subunit and two auxiliary β subunits. The expression of the α subunit isoform is developmentally regulated and tissue specific. To date, nine Nav α subunits have been cloned and named Nav1.1-Nav1.9.4-5 Sodium channels in the adult central nervous system and heart contain β1 through β4 subunits, whereas sodium channels in adult skeletal muscle have only the β1 subunit.6
The isoform Nav1.4, is primarily expressed in skeletal muscle.7
Different missense mutations in the gene for the Nav1.4 are correlated with several muscular diseases such as, Paramyotonia congenital (PMC), PMC without cold paralysis, potassium-aggravating myotonia, and hyperkalemic periodic paralysis.8
