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. 2001 May 15;98(11):6482–6487. doi: 10.1073/pnas.111447798

Figure 1.

Figure 1

Extracellular bupivacaine inhibits GIRK1/4 channels. Oocytes were injected with the cRNA for GIRK4-GIRK1 dimer plus the m2 muscarinic receptor. (a) Macroscopic current was recorded continuously by using two-electrode voltage clamp from an oocyte bathed in 95 mM KCl (pH 7.5) with the muscarinic agonist carbachol (0.3 μM; solid bar) and then with carbachol plus 500 μM bupivacaine (gray box). The holding potential (VH) was −80 mV. Dashed line indicates the zero current level. (Right) Coapplication of carbachol and bupivacaine (500 μM). (b) Continuous current recording shows the effect of increasing concentrations of bupivacaine coapplied with carbachol. (c) The carbachol-induced current was normalized (carbachol, I/Io) and plotted as a function of bupivacaine concentration. Smooth curve shows the best fit to the Hill equation, with an apparent Ki of 22 ± 4 μM and a Hill coefficient of 0.68 ± 0.06 (n = 7). (d) Xenopus oocytes injected with the cRNA for GIRK1, GIRK4, and the G protein Gβ1 and Gγ2 subunits. Current responses were elicited by 500-ms voltage step to −80 mV (VH = 0 mV) in 0, 30, 100, or 500 μM bupivacaine. (e) The normalized current (Gβγ, I/Io) was plotted as a function of bupivacaine concentration. Smooth curves show the best fit to the Hill equation for −40 mV (Ki = 170 ± 12 μM; Hill = 0.83 ± 0.04) and −110 mV (Ki = 98 ± 3 μM; Hill = 0.96 ± 0.03).