Effects of mutating residue L211 in S5 on KCa3.1 Pomax. (A) Inside-out current recordings demonstrating that increasing the volume size of the substituting residue at position 211 in S5 has no significant impact on Pomax relative to wild type. A significant increase was, however, observed with the L211F, suggesting possible aromatic–aromatic interactions between L211F and F248. The results of this analysis are presented in the scatter plot illustrated in B, which shows a Pearson correlation coefficient of 0.75 ± 0.15 between the volume size of the residue engineered at 211 and Pomax. (C) A better correlation was obtained between Pomax and the solvation energy of the residue at 211 with a Pearson correlation coefficient of 0.84 ± 0.07. This analysis confirms that L211 can come in close proximity of F248 during gating, as revealed by the Pomax increase seen with the L211F mutant. Recordings were performed in symmetrical 200-mM K2SO4 conditions in saturating internal Ca2+ (25 µM) at a pipette potential of 100 mV. All-point histograms were computed from the entire recording.