Knocking out the glial glutamate transporter GLT-1 reduces glutamate uptake but does not affect hippocampal glutamate dynamics in early simulated ischaemia

Martine Hamann, David J. Rossi, Hélène Marie, David Attwell

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Glutamate release in ischaemia triggers neuronal death. The major glial glutamate transporter, GLT-1, might protect against glutamate-evoked death by removing extracellular glutamate, or contribute to death by reversing and releasing glutamate. Previous studies of the role of GLT-1 in ischaemia have often used the GLT-1 blocker dihydrokainate at concentrations that affect transporters other than GLT-1 and which affect kainate, N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors. In hippocampal slices from postnatal day 14 mice lacking GLT-1, the current response of area CA1 pyramidal cells to superfused AMPA and NMDA (which are not taken up) was unaffected, whereas the response to 100 μM glutamate was more than doubled relative to that in wild-type littermates, a finding consistent with a decrease in glutamate uptake. In response to a few minutes of simulated ischaemia, pyramidal cells in wild-type mice showed a large and sudden inward glutamate-evoked current [the anoxic depolarization (AD) current], which declined to a less inward plateau. In mice lacking GLT-1, the time to the occurrence of the AD current, its amplitude, the size of the subsequent plateau current and the block of the plateau current by glutamate receptor blockers were all indistinguishable from those in wild-type mice. We conclude that GLT-1 does not contribute significantly to glutamate release or glutamate removal from the extracellular space in early simulated ischaemia. These data are consistent with glutamate release being by reversal of neuronal transporters, and with uptake into glia being compromised by the ischaemia-evoked fall in the level of ATP needed to convert glutamate into glutamine.

Original languageEnglish (US)
Pages (from-to)308-314
Number of pages7
JournalEuropean Journal of Neuroscience
Volume15
Issue number2
DOIs
StatePublished - 2002
Externally publishedYes

Fingerprint

Amino Acid Transport System X-AG
Neuroglia
Glutamic Acid
Ischemia
N-Methylaspartate
Isoxazoles
Hippocampal CA1 Region
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
AMPA Receptors
Pyramidal Cells
Kainic Acid
Glutamate Receptors
Extracellular Space
Glutamine
Adenosine Triphosphate

Keywords

  • Anoxic depolarization
  • Dihydrokainate
  • Hypoxia
  • Mouse

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Knocking out the glial glutamate transporter GLT-1 reduces glutamate uptake but does not affect hippocampal glutamate dynamics in early simulated ischaemia. / Hamann, Martine; Rossi, David J.; Marie, Hélène; Attwell, David.

In: European Journal of Neuroscience, Vol. 15, No. 2, 2002, p. 308-314.

Research output: Contribution to journalArticle

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