Voltage-gated sodium channels (Na_V) are essential for the generation of action potentials and for cell excitability¹. Na_V channels are activated in response to depolarization and selectively allow the flow of Na⁺ ions. To date, nine Na_V α subunits have been cloned and named Na_V1.1-Na_V1.9^4-5. The Na_V channels are classified into two groups according to their sensitivity to tetrodotoxin (TTX): TTX-sensitive (Na_V1.1, Na_V1.2, Na_V1.3, Na_V1.4, Na_V1.6 and Na_V1.7) and TTX-resistant (Na_V1.5, Na_V1.8 and Na_V1.9)^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. Na⁺ channels in the adult central nervous system and heart contain β₁ through β₄ subunits, whereas Na⁺ channels in adult skeletal muscle have only the β₁ subunit^6,7.

Na_V1.1, also referred to as SCN1A, is a tetrodotoxin-sensitive channel and is broadly expressed in neurons⁷.

Mutations in Na_V1.1 are associated with at least two forms of epilepsy. Gain-of-function missense mutations are a primary cause of generalized epilepsy with febrile seizures plus (GEFS+). Loss-of-function mutations cause severe myoclonic epilepsy of infancy (SMEI)^8,9.