Glutamate transporters in neurologic disease.

The neurotoxic properties of glutamate were first demonstrated in 1957 by Lucas and Newhouse, who showed that systemic administration of glutamate to infant mice caused retinal degeneration. Over the last 4 decades, a direct correlation between the neuroexcitatory and neurotoxic properties of glutamate has been linked to activation of excitatory amino acid receptors. This overactivation leads to an enzymatic cascade of events ultimately resulting in cell death. Regulation of synaptic transmission and glutamate levels in the synaptic cleft is performed by glutamate transporters. Glutamate transport is a sodiumand potassium-coupled process that is capable of concentrating intracellular glutamate up to 10000-fold compared with the extracellular space. These transporters are located throughout the human central nervous system as well as other tissues. Recent physiologic studies provide evidence that glutamate transporters keep synaptic concentrations of glutamate low enough to prevent receptor desensitization and/or excitotoxicity. New insights into the biology of these transporters suggest that their dysfunction may contribute to neurologic disease.