Premium
Synergistic action of hypoosmolarity and glutamine in inducing acute swelling of retinal glial (Müller) cells
Author(s) -
Karl Anett,
Wurm Antje,
Pannicke Thomas,
Krügel Katja,
ObaraMichlewska Marta,
Wiedemann Peter,
Reichenbach Andreas,
Albrecht Jan,
Bringmann Andreas
Publication year - 2011
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.21095
Subject(s) - glutamine , biology , mitochondrion , biochemistry , neuroglia , adenosine , astrocyte , microbiology and biotechnology , endocrinology , amino acid , central nervous system
High blood ammonia, elevated glutamine, and hyponatremia are pathogenic factors contributing to astrocytic swelling and brain edema in liver failure. We investigated the effects of hypoosmolarity, ammonia, and glutamine on the induction of glial cell swelling in freshly isolated slices of the rat retina. Glutamine, but not ammonia or hypoosmolarity per se , evoked a rapid (within one minute) swelling of retinal glial (Müller) cell bodies under hypoosmotic conditions. Under isoosmotic conditions, glutamine evoked a delayed swelling after 10 min of exposure. The effect of glutamine was concentration‐dependent, with half‐maximal and maximal effects at ∼ 0.1 and 0.5 mM. Glutamine in hypoosmotic solution induced a dissipation of the mitochondrial membrane potential. The effects on the mitochondrial membrane potential and the glial soma size were reduced by (i) agents which inhibit the transfer of glutamine into mitochondria and its hydrolysis there, (ii) inhibition of the mitochondrial permeability transition, (iii) inhibitors of oxidative‐nitrosative stress, and (iv) inhibitors of phospholipase A 2 and cyclooxygenase. Glutamine‐induced glial swelling was also prevented by ATP and adenosine, acting at adenosine A 1 receptors. The data suggest that hypoosmolarity accelerates the swelling‐inducing effect of glutamine on retinal glial cells, and that swelling induction by glutamine is mediated by inducing oxidative‐nitrosative stress, inflammatory lipid mediators, and mitochondrial dysfunction. © 2010 Wiley‐Liss, Inc.