FIG. 2.

Functional anatomy of the N-methyl-d-aspartate glutamate receptor (NMDAR). The NMDAR is a voltage-gated cross-membrane channel permeable to calcium. Under physiological conditions, glutamate (Glu) binds to the agonist site (labeled NMDA) and activates the channel, provided that the co-agonist site (labeled GLY) is occupied by glycine (Gly) or d-serine (D-Ser). Magnesium ions block the channel pore in a voltage-dependent manner, which is also unconditionally blocked by noncompetitive antagonists, ketamine, MK-801, or phencyclidine. A redox regulatory site (labeled Redox), especially in the NR2A subunit, provides modulation by reducing agents such as dithiothreitol (DTT) or glutathione (GSH).