N-methyl-D-aspartate receptor subunit 2A (NR2A)

N-methyl-D-aspartate receptor subunit 2A (NR2A, also known as GluN2A) is one of the four NR2 subunits (NR2A-D) that combine with NR1 subunits to form the heterotetrameric NMDA receptor complex, an excitatory ligand-gated ion channel in the central nervous system[1][2][3][5]. NR2A contains a large extracellular amino-terminal domain (ATD), a ligand-binding domain that binds the neurotransmitter glutamate, a transmembrane domain forming part of the ion channel pore, and an intracellular C-terminal domain involved in signaling and protein interactions[1][2][5]. The NR2A subunit endows NMDA receptors with specific kinetic and pharmacological properties, modulating deactivation time, channel open probability, and sensitivity to Mg²⁺ and Zn²⁺ blockade[1][5]. Functionally, NR2A-containing NMDA receptors are essential for synaptic plasticity, learning, memory formation, and development, and alterations are implicated in a range of neuropsychiatric and neurodegenerative conditions[1][6]. NMDA receptors, including those with NR2A, are important therapeutic targets, though modulation carries notable risks due to their central role in excitatory neurotransmission and neuronal survival[3][5].

Other names

Glutamate receptor ionotropic, NMDA 2AGluN2ANR2AGRIN2A (gene name)

Noncompetitive antagonism at the NMDA receptor channel pore; Competitive antagonism at the glutamate-binding site on NR2A; Allosteric modulation via zinc at the amino-terminal domain[5]; Open-channel block; Inhibition of calcium influx