The recent determination of cryo-EM structures of voltage-gated sodium (Nav)channels has revealed many details of these proteins. However, knowledge of ionic permeation through the Nav pore remains limited. In this work, we performed atomistic molecular dynamics simulations to study the structural features of various neuronal Nav channels based on homology modeling of the cryo-EM structure of the human Nav1.4 channel and, in addition, on the more recent resolved configuration for Nav1.2. In particular, single Na+ permeation events during standard MD runs suggest that the ion resides in the inner part of the Nav selectivity filter (SF). On-the-fly free-energy parametrization (OTFP) temperature accelerated molecular dynamics (TAMD) was also used to calculate two-dimensional free energy surfaces (FESs) related to single/double Na+ translocation through the SF of the Nav1.2 homology model. The same thermodynamic analysis was performed on the cryo-EM based Nav1.2 configuration. These additional simulations revealed distinct mechanisms for single and double Na+ permeation through the wild-type SF, which has a charged lysine in the DEKA ring. In particular, the extracted protein-ion configurations are not accessible by the other modified SFs tested by TAMD/OTFP. Overall, the description of these mechanisms gives us new insights into ion conduction in human Nav cryo-EM based configurations, that could advance understanding of these systems and how they differ from potassium and bacterial Nav channels.