QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (72) Citing Articles via Google Scholar Google Scholar Articles by Poitry, S. Articles by Tsacopoulos, M. Search for Related Content PubMed PubMed Citation Articles by Poitry, S. Articles by Tsacopoulos, M. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB GLUTAMIC ACID HYDROCHLORIDE LACTIC ACID

 Previous Article  |  Next Article 

The Journal of Neuroscience, March 1, 2000, 20(5):1809-1821

Mechanisms of Glutamate Metabolic Signaling in Retinal Glial (Müller) Cells

Serge Poitry¹, Carol Poitry-Yamate¹, Joern Ueberfeld², Peter R. MacLeish³, and Marcos Tsacopoulos¹

¹ Department of Physiology, University of Geneva Medical School, 1211 Geneva 4, Switzerland, ² Department of Applied Physics, University of Geneva, 1211 Geneva 4, Switzerland, and ³ Neuroscience Institute, Morehouse School of Medicine, Atlanta, Georgia 30310-1495

Retinal Müller (glial) cells metabolize glucose to lactate, which is preferentially taken up by photoreceptor neurons as fuel for their oxidative metabolism. We explored whether lactate supply to neurons is a glial function controlled by neuronal signals. For this, we used subcellular fluorescence imaging and either amperometric or optical biosensors to monitor metabolic responses simultaneously from mitochondrial and cytosolic compartments of individual Müller cells from salamander retina. Our results demonstrate that lactate production and release is controlled by the combined action of glutamate and NH₄⁺, both at micromolar concentrations. Transport of glutamate by a high-affinity carrier can produce in Müller cells a rapid rise of glutamate concentration. In our isolated Müller cells, glutamine synthetase (GS) converted transported glutamate to glutamine that was released. This reaction, predominant when enough NH₄⁺ is available, was limited at micromolar concentrations of NH₄⁺, and more glutamate entered then as substrate into the mitochondrial tricarboxylic acid cycle (TCA). Increased production of glutamine by GS leads to increased utilization of ATP, some of which is generated glycolytically. Methionine sulfoximine, a specific inhibitor of GS, suppressed the stimulatory effect of glutamate and NH₄⁺ on glycolysis and induced massive entry of glutamate into the TCA cycle. The rate of glutamine production also determined the amount of pyruvate transaminated by glutamate to alanine. Lactate, alanine, and glutamine can be taken up and metabolized by photoreceptor neurons. We conclude that a major function of Müller glial cells is to nourish retinal neurons and to metabolize the neurotoxic ammonia and glutamate.

Key words: ammonia; glutamine synthetase; biosensor; NADH; fluorescence imaging; lactate; retina

---

Copyright © 2000 Society for Neuroscience  0270-6474/00/2051809-13$05.00/0

This article has been cited by other articles:

				R. Occhipinti, E. Somersalo, and D. Calvetti Astrocytes as the Glucose Shunt for Glutamatergic Neurons at High Activity: An In Silico Study J Neurophysiol, May 1, 2009; 101(5): 2528 - 2538. [Abstract] [Full Text] [PDF]

				S. Arai-Gaun, N. Katai, T. Kikuchi, T. Kurokawa, K. Ohta, and N. Yoshimura Heme Oxygenase-1 Induced in Muller Cells Plays a Protective Role in Retinal Ischemia-Reperfusion Injury in Rats Invest. Ophthalmol. Vis. Sci., November 1, 2004; 45(11): 4226 - 4232. [Abstract] [Full Text] [PDF]

				J. P. M. Wood, G. Chidlow, M. Graham, and N. N. Osborne Energy Substrate Requirements of Rat Retinal Pigmented Epithelial Cells in Culture: Relative Importance of Glucose, Amino Acids, and Monocarboxylates Invest. Ophthalmol. Vis. Sci., April 1, 2004; 45(4): 1272 - 1280. [Abstract] [Full Text] [PDF]

				Y. Akagi, A. Hashigasako, P. Degenaar, S. Iwabuchi, Q. Hasan, Y. Morita, and E. Tamiya Enzyme-Linked Sensitive Fluorometric Imaging of Glutamate Release from Cerebral Neurons of Chick Embryos J. Biochem., September 1, 2003; 134(3): 353 - 358. [Abstract] [Full Text] [PDF]

				I. Zaganas, C. Spanaki, M. Karpusas, and A. Plaitakis Substitution of Ser for Arg-443 in the Regulatory Domain of Human Housekeeping (GLUD1) Glutamate Dehydrogenase Virtually Abolishes Basal Activity and Markedly Alters the Activation of the Enzyme by ADP and L-Leucine J. Biol. Chem., November 22, 2002; 277(48): 46552 - 46558. [Abstract] [Full Text] [PDF]

				L. Carter-Dawson, M. L. J. Crawford, R. S. Harwerth, E. L. Smith III, R. Feldman, F. F. Shen, C. K. Mitchell, and A. Whitetree Vitreal Glutamate Concentration in Monkeys with Experimental Glaucoma Invest. Ophthalmol. Vis. Sci., August 1, 2002; 43(8): 2633 - 2637. [Abstract] [Full Text] [PDF]

				K. Kashiwagi, Y. Iizuka, M. Araie, Y. Suzuki, and S. Tsukahara Effects of Retinal Glial Cells on Isolated Rat Retinal Ganglion Cells Invest. Ophthalmol. Vis. Sci., October 1, 2001; 42(11): 2686 - 2694. [Abstract] [Full Text] [PDF]

				D. Mort, P. Marcaggi, J. Grant, and D. Attwell Effect of Acute Exposure to Ammonia on Glutamate Transport in Glial Cells Isolated From the Salamander Retina J Neurophysiol, August 1, 2001; 86(2): 836 - 844. [Abstract] [Full Text] [PDF]

				S. M. Hutson, E. Lieth, and K. F. LaNoue Function of Leucine in Excitatory Neurotransmitter Metabolism in the Central Nervous System J. Nutr., March 1, 2001; 131(3): 846S - 850. [Abstract] [Full Text]

				S. Gu, H. L. Roderick, P. Camacho, and J. X. Jiang Characterization of an N-system Amino Acid Transporter Expressed in Retina and Its Involvement in Glutamine Transport J. Biol. Chem., June 22, 2001; 276(26): 24137 - 24144. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help