Structure of voltage-gated sodium channels. (a) Schematic representation of the sodium-channel subunits. The α subunit of the Nav1.2 channel is illustrated together with the β1 and β2 subunits; the extracellular domains of the β subunits are shown as immunoglobulin-like folds, which interact with the loops in the α subunits as shown. Roman numerals indicate the domains of the α subunit; segments 5 and 6 (shown in green) are the pore-lining segments and the S4 helices (yellow) make up the voltage sensors. Blue circles in the intracellular loops of domains III and IV indicate the inactivation gate IFM motif and its receptor (h, inactivation gate); P, phosphorylation sites (in red circles, sites for protein kinase A; in red diamonds, sites for protein kinase C); ψ, probable N-linked glycosylation site. The circles in the re-entrant loops in each domain represent the amino acids that form the ion selectivity filter (the outer rings have the sequence EEDD and inner rings DEKA). (b) The three-dimensional structure of the Nav channel α-subunit at 20 Å resolution, compiled from electron micrograph reconstructions. Adapted from . (c) Schematic representation of NaChBac, the bacterial voltage-gated sodium channel.