Fig. 1.

ATP-dependent activation of I_Ks channels. (A) KCNQ1 + KCNE1 (hI_Ks) currents in inside-out patches run down or up in 0 (red), 0.5 (green), and 5 mM (blue) [ATP] from that immediately after patch excision (black, I₀). Voltage pulses were +80 mV from a −80-mV holding potential. (Right) I_t, I₀ tail current amplitudes. (B) ATP dose–response of WT (black) and Q357R (red, also scaled to the WT currents at 20 mM ATP) I_Ks, and fits to the Hill equation (solid curves) with Hill coefficient 1 and 1.1, and EC₅₀ 1.66 and 9.60 mM, respectively. (C) Currents of WT (Left) and Q357R (Center) hI_Ks recorded from inside-out patches and G–V relations after patch excision in solutions containing various [ATP]. Solid curves are fits of Boltzmann equation (Right; Materials and Methods) with V_1/2 (mV) at 0.5, 5, and 20 mM [ATP], respectively: WT, 23.7 ± 3.5 (black), 25.6 ± 3.2 (purple), 25.4 ± 5.0 (blue); Q357R, 53.2 ± 2.5 (red), 30.8 ± 2.6 (green), and 26.2 ± 3.8 (cyan). (D) Normalized ATP dose–response of WT hI_Ks channel activation in control solution [PIP₂] = 100 µM (black), 5 µM PIP₂ (green), 100 µM Ca²⁺ (red), and S27D/S92D hI_Ks in control solution (blue; Materials and Methods). Five and 100 µM [PIP₂] are 50% and 100% of saturation for I_Ks channel activation, respectively (14). Dashed curves in B and C are the fittings of the model in Fig. 7A.