Fig. 1
Structure, architectural elements, and sodium channel (NaV) topology. a Side view of the voltage-gated sodium channel pore forming (alpha) subunit. Each domain is color depicted. Extracellular IG-fold domain of the beta subunit is shown. A sodium ion and tetrodotoxin (TTX), both in orange, are shown outside of the external vestibule. GX-936, a potent and isoform-selective acylsulfonamide, is shown near its DIV voltage-sensor domain (VSD) binding site. The DEKA box represents the selectivity filter comprised of Asp, Glu, Lys, and Ala sidechains. Traditional sodium channel blockers are shown at the intracellular entrance to the of pore domain. b Top view of (a) depicting the four-fold symmetry and central permeation pathway for by the Pore Module (PM) of each domain and voltage-sensing domain (VSD). Note the domain swapped architecture between each PD and VSD, a feature which underlies allosteric coupling in NaV gating. c Classic topology plot showing the same features