Physicochemical properties of LC-CoA esters required for activation of TALK-2 K_2P channels. (A) Chemical structure of LC-CoA (oleoyl-CoA; 18:1). The fatty acid tail is shaded blue. (B) Analyzed current traces at +80 mV of TALK-2 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 3 µM of LC-CoA esters with varying number and position of double bonds (18:0, 18:1, 18:2, 18:3) in the fatty acid tail of the molecule or 5 mg ml⁻¹ BSA. (C) Analyzed current traces at +80 mV of TALK-2 channels, measured as in B, using control bath solution and in the presence of 3 µM LC-CoA esters with varying chain length (14:0, 16:0, 18:0, 22:0) of the fatty acid tail. (D) Fold activation of TALK-2 channels by LC-CoA esters with varying double bonds or chain lengths, measured as in B and C and normalized to the respective Rb⁺-activated current (red; B and C) at +80 mV. Data are summarized in Table S3. The average fold activation by Rb⁺ (I_Rb⁺/I_basal) of TALK-2 WT channels is 12 ± 3 (n = 20). Number of independent experiments is indicated above the bars. All data are presented as mean ± SEM.