A: Schematic of the transmembrane topology of Kir6.2 and SUR1. B: Mean relation between gliclazide concentration and inhibition of the Kir6.2/SUR1 current, measured in inside-out patches
(n = 5–8). The conductance in the presence of gliclazide (G) is expressed as a fraction of its amplitude in the absence of the drug (Gc). The line is fit to (equation 2) G/Gc = (L + (1 − L)/(1 + ([S]/IC50–1)h1)) × (1/(1 + ([S]/IC50–2)h2)), where IC50–1 = 51 nmol/l, h1 = 1.0, IC50–2 = 3.1 mmol/l, h2 = 1, and L = 0.40 (19); [S] is the concentration of sulphonylurea; IC50–1 and IC50–2 are the half-maximal inhibitory concentrations at the high- and low-affinity sites, respectively; h1 and h2 are the Hill coefficients for the high- and low-affinity sites, respectively; and L is the fraction of current that remains unblocked when all high-affinity sites are occupied.