Figure 1.
Features of GluN1/N2 and GluN1/N3 NMDA receptors (NMDAR). NMDARs function as tetramers with four domains in each subunit: extracellular amino-terminal (NTD) and agonist-binding (ABD) domains; transmembrane domain (TMD) forming the ion channel; and an intracellular carboxyl-terminal domain (CTD). The clamshell-like NTD and ABD regulate ion channel activity. Left: GluN1/N2 receptors. Glutamate (GluN2) and glycine (GluN1) binding are required for channel opening. Current flow is also regulated by a voltage-dependent block by extracellular Mg2+. When open and at potentials near the resting membrane potential, GluN1/N2 receptors predominantly produce inward current carried by Na+ and Ca2+ and hence are excitatory. Right: GluN1/N3 receptors are composed of only glycine-binding subunits and display an odd activation mechanism. Glycine binding to GluN3 by itself can activate the receptor whereas binding to GluN1 leads to strong desensitization and inhibition of receptor function. GluN1/N3 receptor mainly conduct inward Na+.