GluN3

GluN3 refers to a family of NMDA receptor subunits encoded by the GRIN3A and GRIN3B genes, commonly called NR3A and NR3B. These subunits can assemble with the obligatory GluN1 (NR1) and GluN2 (NR2) subunits to form NMDA-type ion channels. Compared with conventional GluN1/GluN2 receptors, GluN3-containing receptors display distinct biophysical and pharmacological properties, typically showing reduced calcium permeability and decreased sensitivity to magnesium block, which in turn lowers the overall ionic current for a given ligand stimulus.

GluN3A and GluN3B have different developmental and regional expression patterns. GluN3A is highly expressed in the developing brain and tends to decline with maturation, while GluN3B has a more variable and sometimes more persistent distribution across brain regions. The exact spatial and temporal expression can vary by species and tissue.

Receptors containing GluN3 subunits can form di- or tri-heteromeric assemblies, including combinations with GluN1 and GluN2 subunits. The presence of GluN3 shifts the receptor’s ligand sensitivity and kinetics, and activation commonly involves glycine as a co-agonist, with GluN3 contributing to the receptor’s binding properties. The net effect of GluN3 is typically a dampening of calcium influx through the channel, which is thought to influence synaptic signaling and plasticity.

Functional implications of GluN3-containing receptors are studied in the context of development, synapse formation, plasticity, and neural excitability. Alterations in GluN3 expression have been investigated for potential links to neurodevelopmental and psychiatric conditions, but precise roles remain an active area of research.

Genes GRIN3A and GRIN3B encode GluN3A and GluN3B, respectively, contributing to the diversity of NMDA receptor signaling in the central nervous system.