LIN-Gly and LIN-Tyr have larger voltage shifts but smaller G max increases as compared to LIN. (A) Chemical structures of LIN, LIN-Gly, and LIN-Tyr. (B) Current of WT KCNQ1 with and without 2 µM of LIN-Gly, demonstrating the shift in voltage dependence toward negative voltages (ΔV0.5) and increase in maximal conductance (ΔGmax) effects by addition of PUFA. (C) Current traces of KCNQ1 before and after application of 7 µM of LIN (black), LIN-Gly (green), and LIN-Tyr (blue). (D) ΔV0.5 dose-response curve of LIN (n = 8), LIN-Gly (n = 10), and LIN-Tyr (n = 6). (E) Gmax dose-response curve of LIN (n = 8), LIN-Gly (n = 7), and LIN-Tyr (n = 6). (F) ΔV0.5 effect of LIN (−5.45 ± 0.69 mV; n = 8), LIN-Gly (−25.28 ± 1.69 mV; n = 10), and LIN-Tyr (−44.51 ± 5.05 mV; n = 6) at 7 µM. ANOVA with Tukey’s multiple comparison gave P < 0.0001 between all compounds. (G) Gmax effect of LIN (1.39 ± 0.13; n = 8), LIN-Gly (1.3 ± 0.06; n = 7) and LIN-Tyr (1.01 ± 0.09; n = 6) at 7 µM. ANOVA with Tukey’s multiple comparison gave P < 0.0001 between LIN and LIN-Tyr, P = 0.0005 between LIN-Gly and LIN-Tyr, and P = 0.25 between LIN and LIN-Gly. Data are given as mean ± SEM. LIN data from Yazdi et al. (2021). ***, P < 0.001; ****, P < 0.0001.