Ion channels and the regulation of neurotransmitter glutamate release.

Introduction Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system. There are multiple receptors for glutamate: in addition to the fast transfer of information via the recently cloned receptors for AMPA [(RS)-y-amino-3hydroxy5 -methyl-4-isoxazolepropionate]/kainate [ l ] and the high-affinity kainate receptor [2], Ca+ influx via the post-synaptic N-methyl-i>-aspartate (NMDA) receptor is implicated in memory and learning [ 3 ] . The NMDA receptor, subunits of which have also been cloned [4], is also associated with the excitotoxicity of glutamate released in an uncontrolled fashion during brain ischaemia [ S ] . In addition to these ionotropic receptors, G-protein metabotropic glutamate receptors have been characterized [6] and cloned [4], coupled via phospholipase C to phosphoinositide hydrolysis, and more recently to cyclic AMP regulation [7].