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Figure 10. Comparison of the activatory and inhibitory effects of Mg-nucleotides. (A) Concentration–response relationships for activation and inhibition of macroscopic KATP currents by ADP. Inhibition was measured for Kir6.2/SUR1 currents in the absence of Mg2+ (open circles; n = 6). Activation was measured for Kir6.2-G334D/SUR1 currents in the presence of Mg2+ (filled squares; n = 8; data from Fig. 5 C). Filled circles (n = 15) indicate data obtained for Kir6.2/SUR1 currents in the presence of Mg2+, where activation and inhibition are simultaneously present. The solid lines are the best fit of Eqs. 1–3 to the mean data. For Kir6.2-G334D/SUR1 channels, data were fit with Eq. 1, EC50 = 7.7 µM and h = 1.30. For Kir6.2/SUR1 channels, data in Mg-free solution were fit with Eq. 2, IC50 = 62 µM and h = 0.81, and data in Mg-containing solution were fit with Eq. 3 using fixed activation parameters (EC50 = 8 µM and h2 = 1.3) and a = 2; IC50 = 280 µM and h1 = 1.4 for inhibition. The dotted line is best fit of the data for Kir6.2/SUR1 in Mg-containing solution assuming no interaction between the activatory and inhibitory sites (IC50 was fixed at 62 µM and EC50 at 8 µM) and a = 2.5, h1 = 1.3, and h2 = 1.3. (B) Concentration–response relationships for activation and inhibition of macroscopic KATP currents by ATP. Inhibition was measured for Kir6.2/SUR1 currents in the absence of Mg2+ (open circles; n = 6). Activation was measured for Kir6.2-G334D/SUR1 currents in the presence of Mg2+ (filled squares; n = 8; data from Fig. 5 C). Filled circles (n = 8) indicate data obtained for Kir6.2/SUR1 currents in the presence of Mg2+, where activation and inhibition are simultaneously present. For Kir6.2-G334D/SUR1 channels, the line through the mean data were fit with Eq. 1, EC50 = 112 µM and h = 1.25. For Kir6.2/SUR1 channels in the absence of Mg2+, the line through the mean data are the best fit of Eq. 2, with IC50 = 7.1 µM and h = 1.1. For Kir6.2/SUR1 channels, data in Mg-containing solution were fit with Eq. 2, with IC50 = 14 µM and h = 1.0. (C) Concentration–inhibition relationships for Kir6.2/SUR1-KAKA currents in the absence (open circles; n = 8) and presence of Mg2+ (gray circles; n = 8). The lines through the mean data are the best fit of Eq. 2, with IC50 = 4.8 µM and h = 1.2 for Mg2+-free solution, and IC50 = 8.3 µM and h = 1.2 for Mg2+ solution. (D) Concentration–response inhibition relationships for Kir6.2/SUR1 currents in the absence (open circles; n = 8) or presence of Mg2+ (filled circles; n = 8). The physiological range of [ATP]i is shown by the bar. The lines are drawn by eye. Image published in: Proks P et al. (2010) © 2010 Proks et al. This image is reproduced with permission of the journal and the copyright holder. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike license Larger Image Printer Friendly View

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