PIP₂ regulation of K_2P channels. (A) Fold activation (blue) and inhibition (percent; orange) of K_2P channel currents by 10 µM PIP₂ at +40 mV, measured in ramp protocols as shown in B and C. Insensitive channels are highlighted in gray. Number of independent experiments is indicated next to the bars. Data are summarized in Table S1. (B and C) Representative current traces (right) and analyzed currents at +40 mV plotted over time (left) of THIK-1 (B) and TASK-1 (C) channels measured in voltage ramps between −80 and +80 mV in excised inside-out patches of Xenopus oocytes using control bath solution and in the presence of 10 µM PIP₂. (D) Analyzed TASK-2 currents at +40 mV plotted over time, measured as in B and C, using control bath solution and in the presence of 0.1 µM or 10 µM PIP₂. Current rundown is indicated with an arrow. Low PIP₂ concentration (0.1 µM) rescues current rundown (right) but produces no inhibition (middle); 10 µM PIP₂ also rescues rundown if present (left) but leads to a subsequent inhibition of the channel. If no rundown is present, 10 µM PIP₂ only leads to inhibition (middle). All data are presented as mean ± SEM. n. d., not determined.