FIGURE 4.

The A1899 binding site includes residues of the M2 and M4 segment and the selectivity filter. A–F, mutant TASK-1 channels were expressed in Xenopus oocytes, and block by 400 nm A1899 was analyzed. A and D, sample current traces for wild-type TASK-1 and mutated channels before (black) and after (gray) application of 400 nm A1899. B, C, E, and F, mutant TASK-1 channels with a reduced sensitivity to A1899 indicate residues as part of the binding site for A1899 (illustrated as striated bars). Threonine residues of the P1 and P2 pore loops are part of the A1899 binding site. In the M2 and M4 segment, residues of the binding site are located at a distance of 3–4 amino acids.