Abstract
The plasma membrane transporters for the neurotransmitter glutamate belong to the solute carrier 1 family. They are secondary active transporters, taking up glutamate into the cell against a substantial concentration gradient. The driving force for concentrative uptake is provided by the cotransport of Na+ ions and the countertransport of one K+ in a step independent of the glutamate translocation step. Due to eletrogenicity of transport, the transmembrane potential can also act as a driving force. Glutamate transporters are expressed in many tissues, but are of particular importance in the brain, where they contribute to the termination of excitatory neurotransmission. Glutamate transporters can also run in reverse, resulting in glutamate release from cells. Due to these important physiological functions, glutamate transporter expression and, therefore, the transport rate, are tightly regulated. This review summarizes recent literature on the functional and biophysical properties, structure–function relationships, regulation, physiological significance, and pharmacology of glutamate transporters. Particular emphasis is on the insight from rapid kinetic and electrophysiological studies, transcriptional regulation of transporter expression, and reverse transport and its importance for pathophysiological glutamate release under ischemic conditions.
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This work was supported by the National Institutes of Health grant 2R01NS049335-06A1 awarded to CG and a Binational Science Foundation (BSF), grant 2007051 awarded to CG and B. I. Kanner.
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Grewer, C., Gameiro, A. & Rauen, T. SLC1 glutamate transporters. Pflugers Arch - Eur J Physiol 466, 3–24 (2014). https://doi.org/10.1007/s00424-013-1397-7
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DOI: https://doi.org/10.1007/s00424-013-1397-7