Glutamate ionotropic receptor NMDA type subunit 2C (GRIN2C) (GRIN2C)

The Glutamate ionotropic receptor NMDA type subunit 2C (GRIN2C) is a fundamental component of the N-methyl-D-aspartate (NMDA) receptor complex, which functions as a heterotetrameric, ligand-gated ion channel in the central nervous system (UniProt: Q14957). This subunit is uniquely characterized by its high expression levels in the cerebellum, particularly within the granule cells, where it contributes to the modulation of excitatory neurotransmission and synaptic plasticity (PubMed: 25339738). Biophysically, receptors containing the GRIN2C subunit exhibit distinct properties, including a reduced sensitivity to magnesium-dependent block and lower single-channel conductance compared to those containing 2A or 2B subunits (NCBI Gene: 2905). These characteristics allow GRIN2C to play a specialized role in maintaining tonic NMDA receptor activity and supporting long-term depression (LTD) in cerebellar circuits.\n\nIn the context of human health, genetic variations and altered expression of GRIN2C have been associated with several neuropsychiatric conditions, most notably schizophrenia and bipolar disorder (PubMed: 15505651). The subunit is also implicated in neurodevelopmental disorders and may play a role in the pathophysiology of Parkinson's disease. Pharmacologically, while many traditional NMDA receptor antagonists like ketamine and memantine are non-selective, there is significant research into developing subunit-selective modulators (PubMed: 20810946). Selective negative allosteric modulators (NAMs) and positive allosteric modulators (PAMs) targeting GRIN2C are being explored for their potential to treat cognitive deficits and motor dysfunction while avoiding the broad side effects associated with global NMDA receptor inhibition.

Other names

NR2CGluN2CNMDAR2CGlutamate receptor subunit epsilon-3N-methyl-D-aspartate receptor subunit 2C

Non-competitive antagonism, Positive allosteric modulation, and Negative allosteric modulation of the NMDA receptor complex (PubMed: 20810946).