PNDM mutations reduce channel inhibition by _ATP. (A) Schematic of the mixture of channels with different subunit compositions expected when WT and mutant Kir6.2 are coexpressed (as in the heterozygous state). The relative numbers of the channel types expected if WT and mutant subunits segregate independently (i.e., follow a binomial distribution) are indicated above the figure. The circle indicates the only channel type predicted to show a substantial change in _ATP sensitivity if the mutation affects _ATP binding (see text). (B) Mean relationship between [_ATP] and K_ATP current (G), expressed relative to the conductance in the absence of nucleotide (GC) for Kir6.2/SUR1 (red, n = 6) and heterozygous (black, n = 6) and homomeric (blue, n = 6) Kir6.2-R201H/SUR1 channels. The smooth curves are the best fit to the Hill equation. The IC50 was 7 μM, 12 μM, and 300 μM for WT, heterozygous R201H, and homomeric R201H channels, respectively. Data were obtained in the absence of Mg²⁺. Part B reproduced with permission from Proceedings of the National Academy of Sciences of the United States of America (83). (C) Mean relationship between [Mg_ATP] and K_ATP current, expressed relative to the conductance in the absence of nucleotide for Kir6.2/SUR1 (red, n = 6) and heterozygous Kir6.2-R201H (black, n = 5) and heterozygous Kir6.2-I296L/SUR1 (blue, n = 5) channels. The smooth curves are the best fit to the Hill equation. The IC50 was 13 μM, 140 μM, and 50 μM for WT, heterozygous R201H, and heterozygous I296L channels, respectively. Data in C are from refs. 33 and 84.