Identification of a molecular target for glutamate regulation of astrocyte water permeability
2008 (English)In: Glia, ISSN 0894-1491, E-ISSN 1098-1136, Vol. 56, no 6, 587-596 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2008. Vol. 56, no 6, 587-596 p.
aquaporin, water channel, swelling, metabotropic glutamate receptors, brain edema, protein-kinase-ii, brain edema, membrane domains, ischemic brain, glial-cells, aquaporin-4, mice, homeostasis, transport, channels
Neurosciences Cell Biology Cell and Molecular Biology
IdentifiersURN: urn:nbn:se:kth:diva-17445DOI: 10.1002/glia.20627ISI: 000254816000001ScopusID: 2-s2.0-45549097641OAI: oai:DiVA.org:kth-17445DiVA: diva2:335489
QC 201507242010-08-052010-08-052015-07-24Bibliographically approved