Figure 3. The effect of PD168077 on NMDAR currents was dependent on PKA–PP1, but not PKC or PLC. A, Plot of peak NMDAR currents showing that application of the membrane-permeable myristoylated PKA inhibitor PKI[14–22] (1μm) reduced NMDAR currents and occluded the effect of subsequent application of PD168077 (20 μm). B, Plot of peak NMDAR currents showing that dialysis with the PLC inhibitor U73122 (5 μm) did not prevent the PD168077-induced reduction of NMDAR currents. Inset, Representative current traces (at time points denoted by #). Calibration: 0.25 nA, 0.5 sec. C, Cumulative data (mean ± SEM) showing the percentage reduction of NMDAR currents by PD168077 in the absence (n = 8) or presence of cpt-cAMP (50μm; n = 9), PKI (PKI[5–24]: 20μm, PKI[14–22]: 1μm; n = 20), PKC19–36 (20μm; n = 8), or U73122 (n = 12) (*p < 0.005; ANOVA). D, Plot of peak NMDAR currents showing that the membrane-permeable PP1–2A inhibitor OA (0.5 μm) blocked the ability of PD168077 (20μm) to reduce NMDAR currents. Inset, Representative current traces (at time points denoted by #). Calibration: 0.1 nA, 0.5 sec. E, Cumulative data (mean ± SEM) showing the percentage modulation of NMDAR currents by PD168077 in the absence (n = 17) or presence of OA (0.5 μm; n = 15), pThr35I-1[7–39] (40 μm; n = 17), or microcystin (5 μm; n = 14) (*p < 0.005; ANOVA). F, Plot of peak evoked NMDAR EPSCs as a function of time and agonist application in a neuron dialyzed with the PP1–2A inhibitor microcystin (20μm). Each point represents the average peak (mean ± SEM) of three consecutive NMDAR EPSCs. Microcystin markedly diminished the PD168077 (20μm)-induced reduction of NMDAR EPSCs. Inset, Representative current traces (average of 3 trials) taken from the records used to construct F (at time points denoted by #). Calibration: 20 pA, 40 msec.