HCY effect on NMDAR currents depends on GluN2 subunit composition. A and D: HCY reduced desensitization of all three NMDAR subtypes tested in human embryonic kidney (HEK) cells in a dose-dependent manner. B: GluN2A showed the greatest enhancement in charge transfer ratio with HCY present, followed by GluN2B and GluN2D. A and C: the amplitude of GluN2A responses to glutamate was enhanced by the presence of HCY, again in a dose-dependent manner. A and C: GluN2B, similar to NMDARs in young cultured neurons, showed dose-dependent amplitude reduction by HCY. GluN2D showed no change in peak amplitude at any [HCY]. N for each [HCY] was as follows: for 100 μM = 50 μM l-HCY isomer, 250 μM = 125 μM l-HCY isomer, and 1 mM = 500 μM l-HCY isomer, GluN2A N = 4, 5, 17; GluN2B N = 5, 5, 17; and GluN2D N = 6, 3, 8.