Identification of a molecular target for glutamate regulation of astrocyte water permeability
Astrocytes play a key role for maintenance of brain water homeostasis, but little is known about mechanisms of short‐term regulation of astrocyte water permeability. Here, we report that glutamate increases astrocyte water permeability and that the molecular target for this effect is the aquaporin‐4...
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Published in | Glia Vol. 56; no. 6; pp. 587 - 596 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Hoboken
Wiley Subscription Services, Inc., A Wiley Company
15.04.2008
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Subjects | |
Online Access | Get full text |
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Summary: | Astrocytes play a key role for maintenance of brain water homeostasis, but little is known about mechanisms of short‐term regulation of astrocyte water permeability. Here, we report that glutamate increases astrocyte water permeability and that the molecular target for this effect is the aquaporin‐4 (AQP4) serine 111 residue, which is in a strategic position for control of the water channel gating. The glutamate effect involves activation of group I metabotropic glutamate receptors (mGluR), intracellular calcium release, and activation of calcium/calmodulin‐dependent protein kinase II (CaMKII) and nitric oxide synthase (NOS). The physiological impact of our results is underlined by the finding that mGluR activation increases the rate of hypoosmotic tissue swelling in acute rat hippocampal slices. Cerebral ischemia is associated with an excessive release of glutamate, and in postischemic cerebral edema ablation of AQP4 attenuates the degree of damage. Thus, we have identified AQP4 as the molecular target for drugs that may attenuate the development of brain edema. © 2008 Wiley‐Liss, Inc. |
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Bibliography: | ark:/67375/WNG-BNHXLZHK-S Sällskapet Barnavård Stiftelsen Samariten Nordic Centre of Excellence Programme in Molecular Medicine Persson Family Foundation Märta och Gunnar V. Philipsons Stiftelse Swedish Research Council ArticleID:GLIA20627 istex:4521F7C539943468D59F9D4E0015D30FCD2D62F9 EG and MZ are equal contributors to this study. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0894-1491 1098-1136 1098-1136 |
DOI: | 10.1002/glia.20627 |