Abstract

L-glutamate is the primary excitatory neurotransmitter in the mammalian central nervous system and has also been implicated as a potent neurotoxin. To ensure a high signal-to-noise ratio during synaptic transmission and to prevent neuronal damage that might occur as a result of excessive activation of glutamate receptors, the extracellular glutamate concentration is tightly controlled by glutamate transporters in the plasma membrane of neurons and the surrounding glial cells. Five subtypes of glutamate transporters have been identified and characterized by molecular cloning. Recent studies of glutamate transporters using the genetic knockout strategy indicate that glial, but not neuronal, glutamate transporters play critical roles in maintaining the extracellular glutamate concentrations and are thereby essential for both normal synaptic transmission at the photoreceptor synapses and protection of neurons against glutamate excitotoxicity. This review summarizes the current knowledge on the properties and functional roles of glutamate transporters, focusing on the properties of the anion channel in the transporters, the unexpected localization of these transporters, their role in synaptic transmission and plasticity, and their involvement in the protection of neurons against excitotoxicity.