Rapid and selective ion transport is essential for the generation and regulation of electrical signaling pathways in living organisms. Here, we use molecular dynamics (MD) simulations with an applied membrane potential to investigate the ion flux of bacterial sodium channel NaVMs. 5.9 xc2xb5s simulations with 500 mM NaCl suggest different mechanisms for inward and outward flux. The predicted inward conductance rate of xe2x88xbc27xc2xb13 pS, agrees with experiment. The estimated outward conductance rate is 15xc2xb13 pS, which is considerably lower. Comparing inward and outward flux, the mean ion dwell time in the selectivity filter (SF) is prolonged from 13.5xc2xb10.6 ns to 20.1xc2xb11.1 ns. Analysis of the Na+ distribution revealed distinct patterns for influx and efflux events. In 32.0xc2xb15.9% of the simulation time, the E53 side chains adopted a flipped conformation during outward conduction, whereas this conformational change was rarely observed (2.7xc2xb10.5%) during influx. Further, simulations with dihedral restraints revealed that influx is less affected by the E53 conformational flexibility. In contrast, during outward conduction, our simulations indicate that the flipped E53 conformation provides direct coordination for Na+. The free energy profile (potential of mean force calculations) indicates that this conformational change lowers the putative barriers between sites SCEN and SHFS during outward conduction. We hypothesize that during an action potential, the increased Na+ outward transition propensities at depolarizing potentials might increase the probability of E53 conformational changes in the SF. Subsequently, this might be a first step towards initiating slow inactivation. 