Computational Investigation of Voltage-Gated Sodium Channel β3 Subunit Dynamics

Voltage-gated sodium (Na-v) channels form the basis for the initiation of the action potential in excitable cells by allowing sodium ions to pass through the cell membrane. The Na-v channel alpha subunit is known to function both with and without associated beta subunits. There is increasing evidence that these beta subunits have multiple roles that include not only influencing the voltage-dependent gating but also the ability to alter the spatial distribution of the pore-forming alpha subunit. Recent structural data has shown possible ways in which beta 1 subunits may interact with the alpha subunit. However, the position of the beta 1 subunit would not be compatible with a previous trimer structure of the beta 3 subunit. Furthermore, little is currently known about the dynamic behavior of the beta subunits both as individual monomers and as higher order oligomers. Here, we use multiscale molecular dynamics simulations to assess the dynamics of the beta 3, and the closely related, beta 1 subunit. These findings reveal the spatio-temporal dynamics of beta subunits and should provide a useful framework for interpreting future low-resolution experiments such as atomic force microscopy.