Glutamate [NMDA] receptor subunit epsilon-2 (GRIN2B) (GRIN2B)

The Glutamate [NMDA] receptor subunit epsilon-2 (GRIN2B), also known as GluN2B or NR2B, is a critical subunit of N-methyl-D-aspartate (NMDA) receptors, which are heterotetrameric ligand-gated ion channels permeable to calcium and other cations, requiring both glutamate and glycine/D-serine for activation. It assembles with two GluN1 subunits and another GluN subunit (typically GluN2A or GluN2B) to form functional receptors with high calcium permeability, voltage-dependent magnesium block, and slow deactivation kinetics that contribute to synaptic plasticity, learning, memory, and excitatory neurotransmission in the brain. GRIN2B is expressed prominently in forebrain regions, influencing dendritic patterning, cortical circuit refinement, and experience-dependent plasticity, with its overexpression enhancing cognitive performance in animal models. Dysregulation or mutations in GRIN2B are implicated in neurodevelopmental disorders, epilepsy, schizophrenia, and neurodegenerative diseases due to altered synaptic signaling and excitotoxicity. Selective antagonists targeting the GluN1/GluN2B amino-terminal domain interface, such as ifenprodil, provide negative allosteric modulation, offering potential therapies for pain, depression, and stroke, though challenges include psychotomimetic side effects and ensuring specificity amid receptor subtype diversity.

Other names

N-methyl-D-aspartate receptor subunit 2BNMDAR2BNR2BGluN2BNMDA receptor subunit epsilon 2glutamate receptor ionotropic NMDA 2B

Negative allosteric modulation at GluN1/GluN2B subunit interface, Noncompetitive antagonism, Positive allosteric modulation