Glutamate ionotropic receptor NMDA type subunit 2C (GluN2C)

The NMDA receptor subunit GluN2C (encoded by the GRIN2C gene) is a protein that forms heterotetrameric N-methyl-D-aspartate (NMDA) receptors, which are ligand-gated ion channels essential for excitatory neurotransmission in the central nervous system [1, 2]. Unlike the more ubiquitous GluN2A and GluN2B subunits, GluN2C is highly localized in the cerebellum, thalamus, and certain populations of astrocytes and parvalbumin-positive interneurons [14, 22]. NMDA receptors containing the GluN2C subunit exhibit distinct biophysical properties, including a lower sensitivity to magnesium block and a reduced channel open probability, which allows them to mediate tonic glutamatergic signaling and specific neuronal oscillations like delta waves [9, 12, 18]. Pathologically, GluN2C is implicated in the hypofunction hypothesis of schizophrenia, and rare genetic variants have been linked to epilepsy and late-onset Alzheimer’s disease [3, 4, 9]. Pharmacologically, GluN2C is targeted by uncompetitive antagonists like ketamine and memantine, as well as experimental positive allosteric modulators (PAMs) such as pyrrolidinone derivatives, which aim to enhance cognitive function and correct synaptic deficits [6, 26]. Selective modulation of this subunit represents a strategic therapeutic approach to treat neuropsychiatric disorders with potentially fewer psychotomimetic side effects compared to non-selective NMDA receptor modulation [16, 20].

Other names

GRIN2CNR2CNMDAR2CGlutamate [NMDA] receptor subunit epsilon-3Glutamate receptor ionotropic NMDA 2C

Uncompetitive pore blocking, positive allosteric modulation, and competitive antagonism of the NMDA receptor complex to modulate cation (Ca2+ and Na+) influx.