Fig. 5: Interactions of small molecule blocker UCL1684 with KCa2.2.
From: Cryo-EM structures of the small-conductance Ca2+-activated KCa2.2 channel
a Cryo-EM density map refined under C4 symmetry with fitted model of UCL1684_KCa2.2 viewed from the plane of the membrane (left), and from the extracellular side (right). Four KCa2.2 subunits are shown in blue, yellow, green and salmon; CaM is shown in gray; and UCL1684 is shown in magenta. The densities for both the protein and UCL1684 are contoured at σ = 6. b One UCL1684 molecule fitted into its cryo-EM density (magenta) is positioned near the aromatic (Phe244) box at the outer end of the pore. c Representative whole-cell current traces of the KCa2.2_F244S mutant elicited by ramps from −120 mV to 40 mV. d The KCa2.2_F244S mutation abolishes blockade by UCL1684 (500 nM) but retains inhibition by AP14145 (30 μM). e Summary statistics show the KCa2.2_F244S mutant’s responses to UCL1684 and AP14145. Data are shown as mean ± SD of current density values recorded from cells transfected with KCa2.2_F244S (n = 8 cells) in response to the indicated treatments. ****P < 0.0001 compared with control (One-way ANOVA and Tukey’s post hoc tests without adjustments).
