Dual regulation of Ca 2+ ‐dependent glutamate release from astrocytes: Vesicular glutamate transporters and cytosolic glutamate levels

Dual regulation of Ca 2+ ‐dependent glutamate release from astrocytes: Vesicular glutamate... Vesicular glutamate transporters (VGLUTs) are responsible for vesicular glutamate storage and exocytotic glutamate release in neurons and astrocytes. Here, we selectively and efficiently overexpressed individual VGLUT proteins (VGLUT1, 2, or 3) in solitary astrocytes and studied their effects on mechanical stimulation‐induced Ca2+‐dependent glutamate release. Neither VGLUT1 nor VGLUT2 overexpression changed the amount of glutamate release, whereas overexpression of VGLUT3 significantly enhanced Ca2+‐dependent glutamate release from astrocytes. None of the VGLUT overexpression affected mechanically induced intracellular Ca2+ increase. Inhibition of glutamine synthetase activity by L‐methionine sulfoximine in astrocytes, which leads to increased cytosolic glutamate concentration, greatly increased their mechanically induced Ca2+‐dependent glutamate release, without affecting intracellular Ca2+ dynamics. Taken together, these data indicate that both VGLUT3 and the cytosolic concentration of glutamate are key limiting factors in regulating the Ca2+‐dependent release of glutamate from astrocytes. © 2009 Wiley‐Liss, Inc. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Glia Wiley

Dual regulation of Ca 2+ ‐dependent glutamate release from astrocytes: Vesicular glutamate transporters and cytosolic glutamate levels

Glia, Volume 57 (12) – Sep 1, 2009

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Publisher
Wiley
Copyright
Copyright © 2009 Wiley‐Liss, Inc.
ISSN
0894-1491
eISSN
1098-1136
DOI
10.1002/glia.20849
pmid
19191347
Publisher site
See Article on Publisher Site

Abstract

Vesicular glutamate transporters (VGLUTs) are responsible for vesicular glutamate storage and exocytotic glutamate release in neurons and astrocytes. Here, we selectively and efficiently overexpressed individual VGLUT proteins (VGLUT1, 2, or 3) in solitary astrocytes and studied their effects on mechanical stimulation‐induced Ca2+‐dependent glutamate release. Neither VGLUT1 nor VGLUT2 overexpression changed the amount of glutamate release, whereas overexpression of VGLUT3 significantly enhanced Ca2+‐dependent glutamate release from astrocytes. None of the VGLUT overexpression affected mechanically induced intracellular Ca2+ increase. Inhibition of glutamine synthetase activity by L‐methionine sulfoximine in astrocytes, which leads to increased cytosolic glutamate concentration, greatly increased their mechanically induced Ca2+‐dependent glutamate release, without affecting intracellular Ca2+ dynamics. Taken together, these data indicate that both VGLUT3 and the cytosolic concentration of glutamate are key limiting factors in regulating the Ca2+‐dependent release of glutamate from astrocytes. © 2009 Wiley‐Liss, Inc.

Journal

GliaWiley

Published: Sep 1, 2009

References

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