Fig. 1. Simulating the effect of d-AA on NMDAR EPSCs. A, A kinetic model of the NMDAR (Clements et al., 1992; Lester and Jahr, 1992), incorporating the binding and unbinding of d-AA. Rates (m−1sec−1 or sec−1):ka of 5 × 106;k-a of 5; kb of 7 × 106; k-b of 210; α of 91.6; β of 46.5; kd of 8.4; and k-d of 1.8. B, Model prediction of receptor response to an exponentially decaying glutamate concentration transient ([Glu]peak of 1 mm; τdecay of 1 msec; top panel) in “control” conditions (thin black line) and in 70 μmd-AA (thick black line). The d-AA trace is also scaled (thick gray line) to the same amplitude as control. C, As inB, except the glutamate transient is 2 μm, 300 msec. D, Contour plot of the blockade ofd-AA of the simulated EPSC amplitude. [Glu]peak values were 0.001, 0.003, 0.01, 0.03,0.1, 0.3, 1, 3, and 10 mm; τdecay values were 0.1, 0.3, 1, 3, 10, 30, 100, 300, and 1000 msec. All combinations were simulated, resulting in a 9 × 9 array that was used to create the contour map in Igor Pro. E, As in B, except for [Glu]peak of 1 μm and τdecayof 100 msec. F, As in B, but with the glutamate transients from B and Ecombined to drive the simulation. G, As inB, except that the responses from B andE were added in a 1:6 ratio to simulate a multisynapse EPSC.