Figure 2. The primary structures of the subunits of the voltage-gated sodium channels.

Cylinders represent alpha helical segments. Bold lines represent the polypeptide chains of each subunit with length approximately proportional to the number of amino acid residues in the brain sodium channel subtypes. The extracellular domains of the β1 and β2 subunits are shown as immunoglobulin-like folds. □, sites of probable N-linked glycosylation; P in red circles, sites of demonstrated protein phosphorylation by PKA (circles) and PKC (diamonds); green, pore-lining segments; white circles, the outer (EEEE) and inner (DEKA) rings of amino residues that form the ion selectivity filter and the tetrodotoxin binding site; yellow, S4 voltage sensors; h in blue circle, inactivation particle in the inactivation gate loop; blue circles, sites implicated in forming the inactivation gate receptor (Catterall, 2000). Sites of binding of α- and β-scorpion toxins and a site of interaction between α and β1 subunits are also shown. Tetrodotoxin is a specific blocker of the pore of sodium channels (Hille, 1975b), whereas the α- and β-scorpion toxins block fast inactivation and enhance activation, respectively, and thereby generate persistent sodium current that causes depolarization block of nerve conduction (Catterall et al., 2007). Tetrodotoxin has been used as a tool to probe the pore of the sodium channel, whereas the scorpion toxins have been valuable as probes of voltage sensor function.