Internal pore dimensions of open and closed transmembrane domains. (a) The open NavMs (in blue ribbon depiction). (b) The closed CavAb (in orange ribbon depiction). The inner surface dimensions as calculated using HOLE (Smart et al., 1996) are shown in dark blue, where the dimensions are sufficient to enable passage of fully hydrated sodium ions, in green where the dimensions are compatible with at least partially dehydrated ions, and red where the dimensions are too narrow to allow passage of sodium ions. Throughout the length of the pore from the extramembranous vestibule area, through the SF, into the bulbous hydrophobic cavity, which binds channel blocker compounds, until ∼14 Å from the intracellular surface, both open and closed structures are very similar and can accommodate sodium ions. However, near the exit of the pore, the closed pore narrows substantially, whereas the open pore retains a clear passage for the ions to exit the transmembrane region of the channel.