ABSTRACT
Glutamate is the major excitatory neurotransmitter in the central nervous system and, like other neurotransmitters, interacts with specific receptors that are of two major types: ionotropic receptors and metabotropic receptors (1,2). The iono tropic receptors have been classified based on their pharmacological and physio logical properties as A-methyl-D-aspartate (NMDA), kainate, and a-amino-3hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors. Activation of the NMDA receptors leads to influx of large quantities of Ca2+ and Na+, which nor mally serve as the physiological trigger signal leading to cell depolarization, but under overstimulation of the NMDA receptor inappropriately high concentrations of Ca2+ are reached intracellularly leading to interference with mitochondrial function and overactivation of Ca2+-dependent cellular enzymes [reviewed in Refs. 2 and 3], including nitric oxide synthase (NOS) in nerve cells containing this enzyme, which causes increased production of NO (4,5). Thus, the toxicity of glutamate is explained to a great extent in terms of the overload of Ca2+ it produces in the cell and the consequences of that overload (6).
