Glutamate [NMDA] Receptor (NMDAR)

The glutamate [NMDA] receptor, commonly referred to as the NMDA receptor (NMDAR), is a subtype of ionotropic glutamate receptors that play a central role in excitatory neurotransmission in the mammalian brain. It is named for its selective activation by N-methyl-D-aspartate (NMDA), a synthetic agonist. The NMDA receptor is crucial for synaptic plasticity, learning, and memory formation and has been implicated in both physiological processes and pathological conditions such as excitotoxicity. The functional NMDA receptor is typically an obligate heterotetramer composed of two glycine-binding GluN1 subunits and two glutamate-binding GluN2 subunits arranged alternately (GluN1–GluN2–GluN1–GluN2). Channel opening requires simultaneous binding of glycine and glutamate along with membrane depolarization to relieve Mg²⁺ block within the channel pore. Once activated, NMDARs allow Ca²⁺ influx along with Na⁺ entry and K⁺ efflux—this high calcium permeability distinguishes them from other iGluRs. Alterations or mutations affecting NMDA receptors are linked to several neurological disorders including epilepsy, schizophrenia, intellectual disability syndromes like anti-NMDA-receptor encephalitis. Excessive activation contributes directly to neuronal injury during ischemic events such as stroke due to calcium overload-induced cell death pathways.

Other names

NMDA receptorN-methyl-D-aspartate receptorGluN receptor

Channel opening requires simultaneous binding of glycine and glutamate along with membrane depolarization to relieve Mg²⁺ block within the channel pore. Once activated, NMDARs allow Ca²⁺ influx along with Na⁺ entry and K⁺ efflux.