G.P. Gasic and M. Hollmann (1992).
Molecular neurobiology of glutamate receptors.
Annual Review of Physiology 54: 507-536.
doi: 10.1146/annurev.ph.54.030192.002451
Excitatory amino acid receptors are currently regarded as the principal neurotransmitter receptors that mediate synaptic excitation in the vertebrate central nervous system (CNS). The first demonstration that acidic amino acids could act as excitatory neurotransmitters dates to the early 1950s and arose from experiments in which monosodium glutamate topically applied to motor cortex caused tonic convulsions (91). Subsequently, experiments with single spinal cord and CNS neurons illustrated the direct depolarizing action of L-glutamate (Glu) and L-aspartate (70). Despite the considerable enthusiasm generated by the initial flurry of discoveries, a long period of skepticism about the possible transmitter role for these amino acids followed. Glu was deemed to have "too ubiquitous" a distribution and a rather high concentration in the brain to be a neurotransmitter. Today, Glu essentially satisfies the four main criteria for classification as a neurotransmitter: (a) presynaptic localization; (b) specific release by physiological stimuli in concentrations sufficiently high enough to elicit a postsynaptic response; (c) identical action to the endogenous transmitter including response to antagonists; and (d) the existence of mechanisms to terminate transmitter action rapidly (70, 152).
This review focuses primarily on the physiology and molecular biology of the ionotropic non-NMDA receptors and the metabotropic ACPD receptor(s) since several of these receptor subunits have been characterized at the molecular level. Due to space limitations, some important physiological studies may not be cited. Properties of the cloned GluR subunits expressed in oocytes and mammalian cell lines are compared and contrasted to GluR receptors expressed in neurons. The computational potential of the NMDA receptor is briefly described and difficulties in cloning this receptor are discussed.