Net glutamate release from astrocytes is not induced by extracellular potassium concentrations attainable in brain.
Elevated extracellular potassium concentration ([K+]e) has been shown to induce reversal of glial Na+-dependent glutamate uptake in whole-cell patch clamp preparations. It is uncertain, however, whether elevated [K+]e similarly induces a net glutamate efflux from intact cells with a physiological intracellular milieu. To answer this question, astrocyte cultures prepared from rat and mouse cortices were incubated in medium with elevated [K+]e (by equimolar substitution of K+ for Na+), and glutamate accumulation was measured by HPLC. With [K+]e elevations to 60 mM, medium glutamate concentrations did not increase during incubation periods of 5-120 min. By contrast, 45 min of combined inhibition of glycolytic and oxidative ATP production increased medium glutamate concentrations 50-100-fold. Similar results were obtained in both rat and mouse cultures. Studies were also performed using astrocytes loaded with the nonmetabolized glutamate tracer D-aspartate, and parallel results were obtained; no increase in medium D-aspartate content resulted from [K+]e elevation up to 90 mM, whereas a large increase occurred during inhibition of energy metabolism. These results suggest that a net efflux of glutamate from intact astrocytes is not induced by any [K+]e attainable in brain.
Longuemare
M C
MC
Department of Neurology, University of California and Veterans Affairs Medical Center, San Francisco 94121, USA.
Swanson
R A
RA
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003470:Culture Media; D004734:Energy Metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D006019:Glycolysis; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D011188:Potassium / Q000008:administration & dosage* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D003470:Culture Media; D018698:Glutamic Acid; D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase; D011188:Potassium