Figure 6.

Molecular determinants for fasudil sensitivity. (A) K_v7 cartoon diagram. Transmembrane segments are labelled S1–S6. Alignment of the pore regions of K_v7.1 to K_v7.5 (KCNQ1–5). RTG binding sites are labelled with the violet band, and residues that are different between K_v7.4/K_v7.5 versus K_v7.2/K_v7.3 in the S5 segment and pore region are labelled with a yellow band. Residues Gly³⁰², Ala³⁰⁴, Leu³⁰⁶ and Ile³⁰⁸ in the S6 segment are labelled with blue or red band. (B) Docking result for the binding of fasudil within the pore domain of K_v7.4 (KCNQ4) channel. Two subunits are shown (yellow and red) of energy‐optimized homology models of the K_v7.4 pore domain derived from the crystal structures of KcsA. The hydrogen bond between fasudil and Ile³⁰⁸ in K_v7.4 (KCNQ4) channel is shown as a blue dotted line. Residue I308 is shown in blue. (C–E) The time courses for the effects of fasudil (30 μM) and RTG (10 μM) on K_v7.4 point mutants recorded at −60 mV. Each mutation site was indicated in (A). (F) Histogram shows the effect of fasudil (30 μM) and RTG (10 μM) on the tail currents of K_v7.4 point mutants (−60 mV). *P < 0.05 compared with the K_v7.4 wildtype currents in the presence of fasudil, #P < 0.05 compared with the K_v7.4 wildtype currents in the presence of RTG, n = 5–8 (one‐way ANOVA, Bonferroni post hoc test).