Fig. 1: Prokaryotic VGSCs are structurally simpler compared to eukaryotic VGSCs but share basic functional architecture.

a Basic topology in the membrane of a single chain of the prokaryotic VGSC NavMs, showing the transmembrane helices (labelled 1-6 for helices S1-S6) which forms one domain of the homotetrameric channel, (top left), next to the single chain of the eukaryotic VGSC Nav1.4 which forms all 4 domains (top right) (b) Four individual subunits of NavMs produce the functional homotetrameric channel in a domain-swapped arrangement (a single domain coloured in deeper blue), c Nav1.4 folds from the single chain to form the functional pseudo-tetrameric channel.