- Peptide GHSHDVTERELRN(C), corresponding to amino acid residues 41-53 of rat NR2A (Accession Q00959). Extracellular, N-terminus.
- Rat brain lysate (1:400 – 1:600).
- Western blot analysis of rat brain lysates:1. Anti-NMDAR2A (GluN2A) (extracellular) Antibody (#AGC-002), (1:600).
2. Anti-NMDAR2A (GluN2A) (extracellular) Antibody, preincubated with NMDAR2A/GluN2A (extracellular) Blocking Peptide (#BLP-GC002).
- Rat brain lysate (3 μg).
- Rat and mouse brain sections.
- Live intact rat C6 glioma cells (1:100).
The NMDA receptors are encoded by seven genes: one NMDAR1 (or NR1) subunit, four NR2 (NR2A-NR2D) and two NR3 (NR3A-NR3B) subunits. The functional NMDA receptor appears to be a heterotetramer composed of two NMDAR1 and two NMDAR2 subunits. Whereas the NMDAR2 subunits that assemble with the NMDAR1 subunit can be either of the same kind (i.e. two NMDAR2A subunits) or different (one NMDAR2A with one NMDAR2B). NMDAR3 subunits can substitute the NMDAR2 subunits in their complex with the NMDAR1 subunit.
The NMDAR is unique among ligand-gated ion channels in that it requires the simultaneous binding of two obligatory agonists: glycine and glutamate that bind to the NMDAR1 and NMDAR2 binding sites respectively. Another unique characteristic of the NMDA receptors is their dependence on membrane potential. At resting membrane potentials the channels are blocked by extracellular Mg2+. Neuronal depolarization relieves the Mg2+ blockage and allows ion influx into the cells. NMDA receptors are strongly selective for Ca2+ influx differing from the other glutamate receptor ion channels that are non-selective cation channels.
Ca2+ entry through the NMDAR regulates numerous downstream signaling pathways including long term potentiation (a molecular model of memory) and synaptic plasticity that may underlie learning. In addition, the NMDA receptors have been implicated in a variety of neurological disorders including epilepsy, ischemic brain damage, Parkinson’s and Alzheimer’s disease.
NMDA receptors expression and function are modulated by a variety of factors including receptor trafficking to the synapses and internalization as well as phosphorylation and interaction with other intracellular proteins.
Species reactivity key:
Expression of NR2A in human-induced pluripotent stem cell-derived neurons.Immunocytochemical staining of human-induced pluripotent stem cell-derived neurons using Anti-NMDAR2A (GluN2A) (extracellular) Antibody (#AGC-002). Adapted from Telezhkin, V. et al. (2016) Am. J. Physiol. 310, C250. with permission of The American Physiological Society.