Results for block of Kir1.1 by Mg²⁺ and Na⁺ are simulated with a kinetic model for permeation, with blocker binding to the transmembrane cavity. (A) Fractional block by Mg²⁺ at different voltages and values of [K⁺]_o. (B) Predicted voltage dependence of Mg²⁺ block at 110 and 25 mM [K⁺]_in. (C) Currents with [K⁺]_o = 110 mM (red) or 11 mM (blue) and 110 mM of internal K⁺ with (dashed lines) and without (solid lines) 40 mM Na⁺. Symbols represent data points. Solid lines show predictions of model parameters listed in Table S2. (D) Predicted occupancies of K⁺ ions in the S1/S3 positions (red) and S2/S4 positions (blue) in the absence (solid lines) and presence (dashed lines) of 1 mM Mg²⁺. The black line shows the fraction of unoccupied cavity sites in the absence of Mg²⁺. The green line indicates the fraction of blocked channels.