Glutamate mediates acute glucose transport inhibition in hippocampal neurons.
Although it is known that brain activity is fueled by glucose, the identity of the cell type that preferentially metabolizes the sugar remains elusive. To address this question, glucose uptake was studied simultaneously in cultured hippocampal neurons and neighboring astrocytes using a real-time assay based on confocal epifluorescence microscopy and fluorescent glucose analogs. Glutamate, although stimulating glucose transport in astrocytes, strongly inhibited glucose transport in neurons, producing in few seconds a 12-fold increase in the ratio of astrocytic-to-neuronal uptake rate. Neuronal transport inhibition was reversible on removal of the neurotransmitter and displayed an IC50 of 5 microm, suggesting its occurrence at physiological glutamate concentrations. The phenomenon was abolished by CNQX and mimicked by AMPA, demonstrating a role for the cognate subset of ionotropic glutamate receptors. Transport inhibition required extracellular sodium and calcium and was mimicked by veratridine but not by membrane depolarization with high K+ or by calcium overloading with ionomycin. Therefore, glutamate inhibits glucose transport via AMPA receptor-mediated sodium entry, whereas calcium entry plays a permissive role. This phenomenon suggests that glutamate redistributes glucose toward astrocytes and away from neurons and represents a novel molecular mechanism that may be important for functional imaging of the brain using positron emission tomography.
Porras
Omar H
OH
Centro de Estudios Científicos, Casilla 1469, Valdivia, Chile.
Loaiza
Anitsi
A
Barros
L Felipe
LF
D009327:4-Chloro-7-nitrobenzofurazan / Q000031:analogs & derivatives*; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001692:Biological Transport / Q000502:physiology; D015220:Calcium Channels / Q000502:physiology; D002478:Cells, Cultured; D003847:Deoxyglucose / Q000031:analogs & derivatives*; D005456:Fluorescent Dyes; D005944:Glucosamine / Q000031:analogs & derivatives*; D005947:Glucose / Q000378:metabolism*; D018698:Glutamic Acid / Q000502:physiology*; D006624:Hippocampus / Q000378:metabolism*; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000187:drug effects / Q000502:physiology; D015222:Sodium Channels / Q000502:physiology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D015220:Calcium Channels; D005456:Fluorescent Dyes; D009004:Monosaccharide Transport Proteins; D018091:Receptors, AMPA; D015222:Sodium Channels; C045400:6-deoxy-N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)aminoglucose; D018698:Glutamic Acid; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D003847:Deoxyglucose; D009327:4-Chloro-7-nitrobenzofurazan; D005947:Glucose; C098340:2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose; D005944:Glucosamine