Figure 2. (A and B) Whole-cell basal currents at –80mV showing the effect of cholesterol enrichment on Kir2.1 and on each of the multiple mutants 6Ca and 6Cb on the background of L222I (A) (n = 7–43) and the mutants L222I_Y280F, L222I_D281G and L222I_L282I (B) (n = 7–16). Significant difference is indicated by an asterisk (*p < 0.05). (C) Representative traces of whole-cell basal currents recorded at -80mV/+80mV for L222I_Y280F, L222I_D281G and L222I_L282I mutants in control and in cholesterol-enriched cells. (D) A model of the C-terminus of the cytosolic domain of one subunit of Kir2.1 showing L222 (yellow) in the CD loop, N251 (red) in the EF loop and Y280 (magenta) and L282 (pink) in the GA loop. (E) Surface presentation of the cytosolic domain of Kir2.1 showing the reversal residue chain (dark gray), L222I (yellow), and N251 (red), Y280 (magenta) and L282 (pink).