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Low‐affinity excitatory amino acid uptake in hippocampal astrocytes: A possible role of Na + /dicarboxylate cotransporters
Author(s) -
Talgøy Holten Aleksander,
Christian Danbolt Niels,
Keiko Shimamoto,
Vidar Gundersen
Publication year - 2008
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.20672
Subject(s) - excitatory postsynaptic potential , biology , biochemistry , glutamate receptor , biophysics , glutamate aspartate transporter , aspartic acid , amino acid , astrocyte , transporter , receptor , neuroscience , excitatory amino acid transporter , gene , central nervous system
The excitatory amino acid transporters (EAATs) underlie the so‐called “high affinity” uptake of glutamate, which is well characterized. In contrast, the “low‐affinity” uptake of glutamate remains poorly defined, and it has been discussed whether it may represent a mere in vitro artifact. Here we have visualized “low‐affinity” excitatory amino acid uptake sites by incubating rat hippocampal slices with the glutamate analogue D ‐aspartate in the presence of PMB‐TBOA, which blocks the EAATs. After fixation of the slices, D ‐aspartate taken up into the tissue was localized with the use of light microscopic immunoperoxidase and electron microscopic immunogold methods, exploiting highly specific antibodies against D ‐aspartate. PMB‐TBOA blocked uptake of both low and high exogenous D ‐aspartate concentrations (0.01–1.0 mM) into nerve terminals, as well as the uptake of 0.01 mM D ‐aspartate into astrocytes. Interestingly, there was a residual PMB‐TBOA insensitive uptake of D ‐aspartate in astrocytes at higher exogenous D ‐aspartate concentrations (0.05–1.0 mM), strongly suggesting that astrocytes have “low‐affinity” uptake sites for excitatory amino acid. The PMB‐TBOA insensitive D ‐aspartate uptake in astrocytes was sodium dependent and inhibited by succinate and to certain extent by homocysteate, but not by cystine or DIDS. We suggest that excitatory amino acid is transported into astrocytes in a “low‐affinity” fashion by sodium/dicarboxylate transporters. © 2008 Wiley‐Liss, Inc.