The NMDA receptor (NMDAR) is an ionotropic receptor for glutamate (NMDA is a name of its selective specific agonist). NMDARs play a critical role in synaptic plasticity mechanisms and thus are necessary for several types of learning and memory.

Structure

Each NMDA receptor contains four or five subunits, the exact number has not yet been established unambiguously. The receptor oligomers are formed from members of three gene families. The subunits are called NR1 (sigma, not related to the sigma receptors ), NR2 (epsilon) A-D and NR3 A-C. Each subunit has an extracellular ligand binding domain, which links to the transmembrane ion pore. The most common arrangement contains two NR1 subunits that bind glycine and two NR2 that bind glutamate.

Five NMDA receptor subunits have now been characterized in both rat and mouse brains.

Agonists

A unique feature of NMDA receptor is the requirement for both glutamate and the co-agonist glycine for the efficient opening of the ion channel which is a part of this receptor.

A third requirement is membrane depolarization. A change in electrical potential toward equilibrium between the two sides of the membrane in which the receptor sits will make it more likely that the ion channel in the NMDA receptor will open by expelling the Mg²⁺ ion that blocks the channel from the outside. This property is fundamental to the role of the NMDA receptor in memory and learning, and it has been suggested that this channel is a biochemical substrate of Hebbian learning, which states that "Neurons that fire together, wire together".

Modulators

NMDA receptor is modulated by a number of endogenous and exogenous compounds. Mg²⁺ not only blocks the NMDA channel in a voltage-dependent manner but also potentiates NMDA-induced responses at positive membrane potentials. Na⁺ , K⁺ and Ca²⁺ not only pass through the NMDA receptor channel but also modulate the activity of NMDA receptors. Zn²⁺ blocks the NMDA current in a noncompetitive and a voltage-independent manner. It has been demonstrated that polyamines do not directly activate NMDA receptors, but instead act to potentiate or inhibit glutamate-mediated responses. The activity of NMDA receptors is also strikingly sensitive to the changes in H⁺ concentration, and partially inhibited by the ambient concentration of H⁺ under physiological conditions. regulated by ion channels that are permeable to Ca²⁺, Na⁺, K⁺ and are sensitive to voltage-dependent Mg²⁺ block.

Role

This channel complex contributes to excitatory synaptic transmission at sites throughout the brain and the spinal cord, and is modulated by a number of endogenous and exogenous compounds. NMDA receptors play a key role in wide range of physiologic and pathologic processes.

See also

• Category: NMDA receptor antagonists

External links

• Liu Y, Zhang J., 2000
• Dingledine R et al. 1999, The Glutamate Receptor Ion Channels Pharmacological Reviews Authorative, free review article.
• NMDA receptor pharmacology