Structure and function of the NMDA receptor

Ionotropic glutamate receptors are ligand-gated ion channels that mediate excitatory synaptic transmission in the central nervous system. Based on their structural and pharmacological properties, ionotropic glutamate receptors can be divided into three groups, which include ?-amino-3-hydroxy-5-methyl-4- isoxasolepropionic acid (AMPA) receptors, kainate receptors, and N-methyl-D-aspartate (NMDA) receptors. Historically, these groups were named on the basis of the activating agonist. AMPA and kainate receptors are discussed in the chapter by Mayer. NMDA receptors are distinguished from other ionotropic glutamate receptors by their unique features including requirement for simultaneous binding of the co-agonists glycine and glutamate, voltage-dependent Mg2+ block, and high permeability to Ca2+. NMDA receptors contribute to the slow component of the excitatory postsynaptic current (EPSC) and play key roles in neuronal development, synaptic plasticity, learning, and memory, as well as in a number of pathophysiological conditions including epilepsy, stroke, neurodegenerative diseases (e.g. Parkinson's disease, Huntington's disease and Alzheimer's disease), and psychiatric disorders (e.g. schizophrenia). Therefore, understanding the relationship between structure and function of the NMDA receptor will provide valuable insights into the mechanisms of synaptic transmission, as well as pathophysiology of a number of disorders in the central nervous system. Understanding this relationship will also facilitate the development of therapeutically useful compounds.