Figure 6. Memantine and ketamine differentially alter NMDAR desensitization. A–C, Representative current traces of GluN1/2A receptors activated by 1 mm glutamate during the recovery from desensitization protocol in control (A), in the presence of 3 μm memantine (B), and in the presence of 1.5 μm ketamine (C). Insets at right show current responses to glutamate application with an expanded time scale at the two interapplication intervals labeled 1 (20 s interval; gray, pink, and light blue traces) and 2 (200 s interval; black, red, and blue traces) in control (A), memantine (B), and ketamine (C). Bars above traces indicate time of application of glutamate (black bars), memantine (red bars), and ketamine (blue bars). D, Summary of GluN1/2A receptor recovery from desensitization results in control (black) and in memantine (red) for experiments and for simulations. Closed squares display mean Ipeak normalized to Ipeak after a 200 s interapplication interval. Open squares display the normalized Ipeak simulated by model 2p in control and in memantine. Single or double exponential fits to the time course of recovery from desensitization are shown with solid lines (fits to data) and dashed lines (fits to simulations). E, Summary of GluN1/2A receptor recovery from desensitization results in control (black), memantine (red), and ketamine (blue) experiments. Closed symbols display mean normalized Ipeak. Lines show single or double exponential fits to the time course of recovery from desensitization. Data for inhibition by memantine from D are replotted here. Mean Ipeak at each interapplication interval was compared by one-way ANOVA with Tukey's post hoc analysis. #p < 0.05 between control and memantine; &p < 0.05 between memantine and ketamine. Memantine was significantly different from control and ketamine at each interapplication interval except for 200 s (to which all Ipeak values were normalized). F–H, Representative current traces as in A–C except for GluN1/2B receptors in control (F), 3 μm memantine (G), and 1.5 μm ketamine (H). Insets at right are current traces at expanded time scales at interapplication intervals labeled 1 (5 s interval; gray, pink, and light blue traces) and 2 (200 s interval; black, red, and blue traces). I, As in E, except for GluN1/2B receptors. Mean Ipeak at each interapplication interval was compared by one-way ANOVA with Tukey's post hoc analysis. +p < 0.05 between control and ketamine; &p < 0.05 between memantine and ketamine. J, Mean τ or τw from fits of the time course of recovery from desensitization. ★★p < 0.01 and ★★★p < 0.001 by one-way ANOVA with Tukey's post hoc analysis. n = 5–11 cells in each group.