Fig. 2: Effect of (R)-L3 on hK_v7.1 in high K⁺ and Rb⁺ buffer.

a, b Representative current traces in 100 mM K⁺ (a) and 100 mM Rb⁺ (b) before (black; ctrl) and after (gray; +(R)-L3) addition of 1 µM (R)-L3. c Activation of hK_v7.1 channel currents by 1 µM (R)-L3 expressed as percent change in current in high K⁺ and Rb⁺ (n = 18 for K⁺, n = 17 for Rb⁺) compared to activation measured in ND96 (n = 30). Significance of mean differences was evaluated by one-way ANOVA and posthoc mean comparison Tukey test (ns for p > 0.05, *p < 0.05). d, e Current-voltage relationship for hK_v7.1 expressing oocytes in the absence (black, n = 18 for K⁺ and Rb⁺) and presence (gray, n = 17 for K⁺, n = 18 for Rb⁺) of 1 µM (R)-L3 in 100 mM K⁺ (d) and 100 mM Rb⁺ (e). V_1/2 values were determined from normalized peak tail currents at −120 mV for each oocyte and fitted to Boltzmann equation. f, g Slow deactivation component of hK_v7.1 in high K⁺ (f) and high Rb⁺ (g) in the absence (black; n = 15 for K⁺, n = 18 for Rb⁺) and the presence (gray; n = 9 for K⁺ and n = 18 for Rb⁺) of (R)-L3. Time constants τ_{slow deact} were determined by two-component exponential fit for each oocyte and voltage step. h Depiction of KCNQ1 in activated state (AO, derived from Kuenze et al³⁸. Amino acids crucial for (R)-L3 activity (magenta) are located at the lower S5 (green) and S6 (blue) helix. Most side chains of the crucial amino acids are orientated to the S4S5 Linker (orange) and VSD (yellow) of an adjacent KCNQ1 subunit.