Figure 8.

Comparison of NR1/2D and cortical receptor modeling results. A, Schematic energy profiles for Mg_o²⁺ interaction with NR1/2D (red line) and cortical (black line) receptors. Rate theory was used to estimate barrier heights and well depths from the equation ΔG_i = −ln(k_i/(6.11 × 10¹² s⁻¹)), where ΔG_i is the plotted Gibbs free energy difference between two states (units of RT, where R is the gas constant and T is absolute temperature) and k_i is the rate constant for transitions between the states (Li-Smerin and Johnson, 1996; Hille, 2001). By convention, a [Mg²⁺] of 1 m is assigned the 0 energy state. Although fraught with inaccuracies (Nonner et al., 1999), rate theory estimates of energy profiles allow useful visual comparisons of kinetic data (Miller, 1999). Electrical depths (x-axis) are taken from Table 1. The dotted lines indicate regions in which the energy profile is unaddressed by the current data; the Mg²⁺ binding site on the internal side of cortical receptors (Johnson and Ascher, 1990), e.g., is not shown. B, Model predictions of Mg_o²⁺ blocking (left) and un- blocking (right) rates are plotted for the indicated receptors and solutions. NR1/2D receptor predictions from the NR1/2D model; cortical receptor predictions from model of Antonov and Johnson (1999). k₋ is sum of the unblocking rate to the outside and permeation rate. C, D, Predicted NMDA receptor I–V curves in the 140 Na_o⁺/125 Cs_i⁺ solution with 1 mm Mg_o²⁺. I–V curve in 0 Mg was assumed to be linear with a reversal potential of 0 mV. The bottom graphs are blowups of the region near the origin of top graphs. The solid lines show predictions of the NR1/2D model (C; red) or the cortical receptor model from Antonov and Johnson (1999) (D; black), and the dotted lines show predictions of modified models that are identical except with no permeant ion binding sites.