Figure 1.

Voltage-gated sodium channel (VGSC) α and β subunit topology. The pore-forming α subunit is composed of four homologous domains (I–IV), each with six transmembrane segments. The fourth segment in each domain contains the voltage-sensing domain of the channel. The inactivation loop between domains III and IV contains the isoleucine, phenylalanine, and methionine (IFM) domain required for channel inactivation. Up to two β subunits may be associated with VGSCs. β1 and β3 subunits associate noncovalently, whereas β2 and β4 subunits associate via a disulfide link. (From Brackenbury and Isom 2011; reprinted, with permission, © Frontiers Media SD.)