Retinal glutamate transporter activity persists under simulated ischemic conditions

Natalie D. Bull, Nigel L. Barnett

Research output: Contribution to journalArticleResearchpeer-review

11 Citations (Scopus)

Abstract

Elevated extracellular concentrations of the neurotransmitter glutamate are neurotoxic and directly contribute to CNS damage as a result of ischemic pathologies. However, the main contributors to this uncontrolled rise in glutamate are still unconfirmed. It has been reported that the reversal of high-affinity glutamate transporters is a significant contributing factor. Conversely, it has also been observed that these transporters continue to take up glutamate, albeit at a reduced saturation concentration, under ischemic conditions. We sought to determine whether glutamate transporters continue to remove glutamate from the extracellular space under ischemic conditions by pharmacologically modulating the activity of high-affinity retinal glutamate transporters during simulated ischemia in vitro. Retinal glutamate transporter activity was significantly reduced under these ischemic conditions. The suppression of retinal glutamate transporter activity, with the protein kinase C inhibitor chelerythrine, significantly reduced ischemic glutamate uptake and enhanced retinal neurodegeneration. These findings imply a limited but protective role for retinal glutamate transporters under certain ischemic conditions, suggesting that pharmacological enhancement of high-affinity glutamate transporter activity may reduce tissue damage and loss of function resulting from toxic extracellular glutamate concentrations.

Original languageEnglish
Pages (from-to)590-599
Number of pages10
JournalJournal of Neuroscience Research
Volume78
Issue number4
DOIs
Publication statusPublished - 15 Nov 2004
Externally publishedYes

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Amino Acid Transport System X-AG
Glutamic Acid
Protein C Inhibitor
Poisons
Extracellular Space
Protein Kinase Inhibitors
Protein Kinase C
Neurotransmitter Agents
Ischemia
Pharmacology
Pathology

Cite this

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Retinal glutamate transporter activity persists under simulated ischemic conditions. / Bull, Natalie D.; Barnett, Nigel L.

In: Journal of Neuroscience Research, Vol. 78, No. 4, 15.11.2004, p. 590-599.

Research output: Contribution to journalArticleResearchpeer-review

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