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. 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 Na⁺ 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_Vβ4 has been associated with Long QT syndrome⁸ and with Huntington's disease, showing a distinct down regulation of Na_Vβ4 in the presymptomatic stage of HD mice, whereas other voltage-gated ion channel subunits were later decreased⁹.