Subtype-specific regulation of K_2P channels by polyanionic lipids. (A) Gating cartoon depicting cross-sectional sketches of K_2P channels indicating the assumed locations of the gates regulated by polyanionic lipids (i.e., PIP₂ and oleoyl-CoA). In TREK-1, TREK-2, and TRAAK channels, the gate is located at the SF and opened by polyanionic lipids. In TASK-1 and TASK-3, the gate is located below the SF (lower gate/X-gate) and closed by polyanionic lipids. Note that the cartoon does not intend to indicate specific binding sites of the lipids. (B) Overview of the subtype-specific lipid effects in K_2P channels: dark blue box, activation; red box, inhibition; light blue box, insensitivity to the lipids with (1) PIP₂ and (2) oleoyl-CoA. The gray box indicates that the respective lipid effect was not determined (n. d.) to be caused by low functional channel expression.