Homology model of hERG from S3b to the S5 pore helix, based on rKv1.2. The model illustrates one subunit between residues S510 and H577. Charged residues are shown in the hERG S3–S4 linker (E518 and E519), the S4 (K525, R528, R531, R534, R537, and K538), and the S4–S5 linker (D540, R541, and E544). Positively charged residues are shown in blue, and negatively charged residues are shown in red. I521, at the extracellular end of S4, is shown in green. Figure was generated using an energy-minimized model (Wynia-Smith et al., 2008) based on the crystal structure of rKv1.2 in the open state.