Molecular dynamics study of ion transport through an open model of voltage-gated sodium channel.

Voltage-gated sodium (NaV) channels are critical in the signal transduction of excitable cells. In this work, we modeled the open conformation for the pore domain of a prokaryotic NaV channel (NaVRh), and used molecular dynamics simulations to track the translocation of dozens of Na+ ions through the channel in the presence of a physiological transmembrane ion concentration gradient and a transmembrane electrical field that was closer to the physiological one than previous studies. Channel conductance was then estimated from simulations on the wide-type and DEKA mutant of NaVRh. Interestingly, the conductivity predicted from the DEKA mutant agrees well with experimental measurement on eukaryotic NaV1.4 channel. Moreover, the wide-type and DEKA mutant of NaVRh exhibited markedly distinct ion permeation patterns, which thus implies the mechanistic difference between prokaryotic and eukaryotic NaV channels.