Retinal glucose metabolism in mice lacking the L-glutamate/aspartate transporter.
The conventional view that glucose is the substrate for neuronal energy metabolism has been recently challenged by the "lactate shuttle" hypothesis in which glutamate cycling in glial cells drives all neuronal glucose metabolism. According to this view, glutamate released by activated retinal neurons is transported into Müller (glial) cells where it triggers glycolysis. The lactate released by Müller cells serves as the energy substrate for neuronal metabolism. Because the L-Glutamate/aspartate transporter (GLAST) is the predominant, Na+-dependent, glutamate transporter expressed by Müller cells, we have used GLAST-knockout (GLAST -/-) mice to examine the relationship between lactate release and GLAST activity in the retina. We found that glucose uptake and lactate production by the GLAST -/- mouse retina was similar to that observed in the wild type mouse retina. Furthermore, addition of 1 mM glutamate and NH4Cl to the incubation medium did not further stimulate glucose uptake in either case. When lactate release was measured in the presence of the lactate uptake inhibitor, alpha-cyano-4-hydroxycinnamate, there was no significant change in the amount of lactate released by retinas from GLAST -/- mice compared to the wild type. Finally, lactate release was similar under both dark and light conditions. These results show that lactate production and release is not altered in retinas of GLAST -/- mice, which suggests that metabolic coupling between photoreceptors and Müller cells is not mediated by the glial glutamate transporter, GLAST.
Sarthy
Vijay P
VP
Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA. vjsarthy@northwestern.edu
Dudley
V Joseph
VJ
Tanaka
Kohichi
K
D027322:Amino Acid Transport System X-AG / Q000172:deficiency / Q000502:physiology*; D000818:Animals; D003624:Darkness; D003847:Deoxyglucose / Q000493:pharmacokinetics; D018698:Glutamic Acid / Q000494:pharmacology; D019344:Lactic Acid / Q000096:biosynthesis; D008027:Light; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012160:Retina / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects
D027322:Amino Acid Transport System X-AG; D019344:Lactic Acid; D018698:Glutamic Acid; D003847:Deoxyglucose