Fig. 1.
V141M KCNQ1 affects activation kinetics and voltage dependence of IKs. a Currents of WT KCNQ1/KCNE1 channels (WT IKs) and heterozygous V141M KCNQ1/KCNE1 channels (V141M IKs) expressed in Xenopus oocytes (left panels). The currents were elicited by test pulses to +60 mV from a holding potential of −100 mV. Tail currents were measured at −40 mV for WT and V141M IKs. The WT and V141M IKs were simulated using a Markov model (right panels; see supplementary materials). b V141M KCNQ1 mutation caused a leftward shift of the conductance–voltage curve (V1/2 = 33.6 ± 4.0 mV for WT, 24.0 ± 1.3 mV for heterozygous V141M; n = 5 for each). Simulation results (solid lines) are consistent with the experimental data (dashed lines). c Voltage dependence of activation and deactivation time constants (τ) of WT and heterozygous V141M IKs (n = 5 for each). τ activation was obtained from fitting the activating current traces with a double exponential function. V141M KCNQ1 causes faster activation of IKs (*p < 0.05 for τ1 and #p < 0.05 for τ2; V141M vs WT; n = 3 for each). d V141M KCNQ1 causes slower deactivation of IKs (*p value <0.05 for τs; V141M (n = 5) versus WT (n = 3). τ deactivation was obtained from fitting the deactivating current traces with a double exponential function. Lines indicate specific τ values for simulations