Hypo-osmotic swelling modifies glutamate-glutamine cycle in the cerebral cortex and in astrocyte cultures.

摘要: In our previous work, we found that perfusion of the rat cerebral cortex with hypo-osmotic medium triggers massive release excitatory amino acid L-glutamate but decreases extracellular levels L-glutamine (R. E. Haskew-Layton et al., PLoS ONE, 3: e3543). The glutamate was linked to activation volume-regulated anion channels, whereas mechanism(s) responsible for alterations in glutamine remained unclear. When mannitol added reverse reductions osmolarity, changes microdialysate were prevented, indicating an involvement cellular swelling. As main source brain is astrocytic synthesis and export, explored impact on transport primary astrocyte cultures. astrocytes, a 40% reduction osmolarity moderately stimulated L-[(3) H]glutamine by ∼twofold produced no uptake. comparison, (traced D-[(3) H]aspartate) more than 20-fold. whole-cell enzymatic assays, discovered caused 20% inhibition conversion H]glutamate into synthetase. Using HPLC assay, further 35% intracellular endogenous glutamine. Overall, findings suggest swelling (i) inhibits synthetase activity, (ii) reduces substrate availability this enzyme because channels. These combined effects likely lead export vivo may partially explain occurrence hyperexcitability seizures human hyponatremia.