Homology modeling of sodium channel VSM. (A) Sequence alignments of VSM from bacterial channels Na_VRh and Na_VAb, and domains I–IV of mammalian sodium channel hNa_V1.4. (B) Homology models of each domain of hNa_V1.4 based on the Na_VAb template, showing relative positions of putative countercharges in S1, S2, and S3 segments, and positively charged residues through R4 in S4 segments. (C) View of homology models in B with S4 residues R1–R3 aligned in each, to show orientation of countercharges to the S4 segment.