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Identification of a molecular target for glutamate regulation of astrocyte water permeability
Author(s) -
Gunnarson Eli,
Zelenina Marina,
Axehult Gustav,
Song Yutong,
Bondar Alexander,
Krieger Patrik,
Brismar Hjalmar,
Zelenin Sergey,
Aperia Anita
Publication year - 2008
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.20627
Subject(s) - astrocyte , glutamate receptor , metabotropic glutamate receptor , biology , aquaporin 4 , metabotropic glutamate receptor 5 , microbiology and biotechnology , nmda receptor , neuroscience , pharmacology , biochemistry , receptor , central nervous system
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.