Mutation effects. (A) Energy landscapes for wild-type KCNQ1 and mutants E160Q, E160A, and E160K at V_m = 0 mV. (B) Comparison of macroscopic current between experiment (black) and simulation (cyan) for homomeric wild-type KCNQ1 and mutants (protocol in inset). (C) I_Ks (KCNQ1+KCNE1) is accurately simulated by slowing S4 movement. Mutations cause further slowing of activation in addition to the KCNE1 effect. Modified from Silva et al. (2009).