NR2Dcontaining

NR2D-containing refers to NMDA receptors that incorporate the NR2D subunit (encoded by GRIN2D). NMDA receptors are ligand-gated ion channels that normally assemble as heterotetramers containing two NR1 subunits and two regulatory NR2 subunits (such as NR2A, NR2B, NR2C, or NR2D). Receptors that include NR2D are collectively called NR2D-containing NMDA receptors.

Functional properties of NR2D-containing receptors distinguish them from other NR2 subtypes. They typically exhibit slower deactivation kinetics and higher affinity for glutamate, which supports longer-lasting calcium influx after glutamate release. They also show a reduced voltage-dependent block by magnesium at resting or near-resting potentials, allowing activity at more negative membrane potentials compared with some other NR2-containing receptors. Their pharmacological profile includes modulation by polyamines and other intracellular signals, and while several compounds show some selectivity, most NMDA antagonists are not exclusively NR2D-specific.

Developmental and regional distribution patterns influence their functional role. NR2D expression is relatively high during early development across various brain regions and persists in specific mature circuits. In the adult brain, NR2D-containing receptors are particularly enriched in areas such as the thalamus, certain cortical interneurons, and specific brainstem nuclei, with regional variation among species and brain regions.

Physiological and clinical relevance is linked to their role in synaptic plasticity, developmental maturation, and network excitability. NR2D-containing NMDA receptors contribute to signaling that shapes synaptic strength and neuronal development. Dysregulation of NMDA receptor function, including NR2D-containing subtypes, has been implicated in neurodevelopmental disorders, epilepsy, chronic pain, and neurodegenerative conditions, making NR2D-containing receptors a target of interest for therapeutic strategies and neuroprotection research.