The generation of action potentials in excitable cells requires different activation kinetics of voltage gated Na (Nav) and K (Kv) channels, with Nav channels activating much faster and allowing the initial Na influx that generates the depolarizing phase. Recent experimental results suggest that the molecular basis for this kinetic difference point to a residue located in the gating pore of the voltage sensor domain, which is a highly conserved isoleucine in Kv channels, but an equally highly conserved threonine in Nav channels. Mutagenesis experiments suggest that the hydrophobicity of this residue in Shaker Kv channels may regulate the energetic barrier that gating charges need to overcame to move through the gating pore, and ultimately the rate of channel opening. In order to quantitatively verify this hypothesis we used a multi-scale modeling approach, consisting in the assessment of the effect of the mutation on charge stabilization within the gating pore using high-resolution molecular dynamics, followed by the incorporation of these results in a lower resolution model of voltage gating to predict the effect of the mutation on the rate of movement of gating charges. The prediction of our modeling approach is fully consistent with the tested hypothesis, thus suggesting that the different activation kinetics of voltage gated Na and K channels originates from a stronger dielectric stabilization exerted by threonine as compared to isoleucine, on the gating charge entering the gating pore.