Retinal glutamate transporter activity persists under simulated ischemic conditions.
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.
Bull
Natalie D
ND
Vision, Touch and Hearing Research Centre, School of Biomedical Sciences, The University of Queensland, Brisbane, Queensland, Australia. n.bull@uq.edu.au
Barnett
Nigel L
NL
D027322:Amino Acid Transport System X-AG / Q000378:metabolism*; D000818:Animals; D026603:D-Aspartic Acid / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005128:Eye Diseases / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D066298:In Vitro Techniques; D007511:Ischemia / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D012160:Retina / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology
D027322:Amino Acid Transport System X-AG; D004791:Enzyme Inhibitors; D018698:Glutamic Acid; D026603:D-Aspartic Acid; D011493:Protein Kinase C