Recent development in NMDA receptors.

PURPOSE: To identify the structure and the function of NMDA receptors, to understand the modulatory mechanism of some endogenous and exogenous compounds on NMDA receptors, and to provide theoretical basis for developing new drugs that modulate NMDA receptors. DATA SOURCES: A total of 24 originally identified articles were selected. STUDY SELECTION: A total of 24 articles were selected from several hundred original articles or reviews. The content of selected articles are in accordance with our purpose and the authors are authorized scientists in the study on NMDA receptors. DATA EXTRACTION: After careful review of the selected papers, the meaningful results and conclusions were extracted using scientific criteria and our experience in the research of NMDA receptors. RESULTS: NMDA receptor contains at least five subunits. They were designated as the NR1 (sigma 1), NR2A (epsilon 1), NR2B (epsilon 2), NR2C (epsilon 3), and NR2D (epsilon 4). A unique feature of NMDA receptor is the requirement for both glutamate and the co-against glycine for the efficient gating. 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. 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. Five NMDA receptor subunits have now been characterized in both rat and mouse brain.