Figure 1.
Effect of PUFA on KCNQ1 channel. (A) Representative example of the effect of PUFA on the KCNQ1 channel, showing a shift in the voltage dependence for channel opening toward negative voltages (ΔV50) and an increase in the maximal conductance (ΔGmax). Curves represent Boltzmann fits to control (black line) and 20 µM of the PUFA LIN (blue). (B) Top view of the xKCNQ1 structure with the pore domain in gray and the voltage-sensing domain in black. xKCNQ1 residues R218 and K316 (corresponding to R228 and K326, respectively, in hKCNQ1) are highlighted in brown and purple, respectively. Previous studies identifying these residues as important for PUFA effects used N-AT and DHA-Gly (Liin et al., 2015; Liin et al., 2018). (C and D) Effect of LIN or STE at indicated free FA (FFA) concentrations on V50 (C) or Gmax (D) of WT hKCNQ1. Data shown as mean ± SEM; n = 5–8 per data point. Concentration-response curves for LIN were fitted using Eq. 2 with the Hill coefficient constrained to either 1 or −1 (see Materials and methods for details). ΔV50,max was constrained to −25 mV to make the fit more robust. ΔV50,max denotes maximal effect in ΔV50; Rel., relative.