Glutamate ionotropic receptor NMDA type subunit 2C (GluN2C) (GluN2C)

Glutamate ionotropic receptor NMDA type subunit 2C (GluN2C) is a specific component of heterotetrameric NMDA receptors, primarily localized in the cerebellum, thalamus, and olfactory bulb (UniProt: Q14957). Unlike the more common GluN2A and GluN2B subunits, GluN2C-containing receptors exhibit unique biophysical properties, such as lower single-channel conductance and a significantly reduced sensitivity to magnesium blockade, which allows them to mediate tonic currents and integrate synaptic inputs over longer periods (PubMed: PMID 25114174). These receptors play a critical role in the pathophysiology of several neuropsychiatric conditions; for instance, reduced GluN2C expression or function is associated with the cognitive deficits and negative symptoms of schizophrenia (PubMed: PMID 30115633). In neurodegenerative diseases like Parkinson's, GluN2C modulation is being investigated for its potential to regulate basal ganglia circuitry. Pharmacological targeting of GluN2C often involves the development of subunit-selective positive allosteric modulators (PAMs) or negative allosteric modulators (NAMs) to fine-tune glutamatergic signaling while minimizing the dissociative side effects typically associated with broad-spectrum NMDA antagonists (PubMed: PMID 25114174). Because of its restricted expression in the cerebellum, drugs targeting this receptor must be carefully evaluated for potential impacts on motor coordination and balance.

Other names

NR2CGRIN2CN-methyl-D-aspartate receptor subunit 2CGlutamate receptor subunit epsilon-3NMDAR2C

Positive allosteric modulation, negative allosteric modulation, and non-competitive channel blockade.