GABA uptake- dependent Ca^sup 2+^ signaling in developing olfactory bulb astrocytes

We studied GABAergic signaling in astrocytes of olfactory bulb slices using confocal Ca2+ imaging and two-photon Na+ imaging. GABA evoked Ca2+ transients in astrocytes that persisted in the presence of GABA(A) and GABA(B) receptor antagonists, but were suppressed by inhibition of GABA uptake by SNAP...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2009-10, Vol.106 (41), p.17570
Main Authors: Doengi, Michael, Hirnet, Daniela, Coulon, Philippe, Pape, Hans-Christian, Deitmer, Joachim W, Lohr, Christian
Format: Article
Language:English
Subjects:
Brain
Calcium
Cells
Neurons
Proteins
Signal transduction
Sodium
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Summary:We studied GABAergic signaling in astrocytes of olfactory bulb slices using confocal Ca2+ imaging and two-photon Na+ imaging. GABA evoked Ca2+ transients in astrocytes that persisted in the presence of GABA(A) and GABA(B) receptor antagonists, but were suppressed by inhibition of GABA uptake by SNAP 5114. Withdrawal of external Ca2+ blocked GABA-induced Ca2+ transients, and depletion of Ca2+ stores with cyclopiazonic acid reduced Ca2+ transients by approximately 90%. This indicates that the Ca2+ transients depend on external Ca2+, but are mainly mediated by intracellular Ca2+ release, conforming with Ca2+-induced Ca2+ release. Inhibition of ryanodine receptors did not affect GABA-induced Ca2+ transients, whereas the InsP3 receptor blocker 2-APB inhibited the Ca2+ transients. GABA also induced Na+ increases in astrocytes, potentially reducing Na+/Ca2+ exchange. To test whether reduction of Na+/Ca2+ exchange induces Ca2+ signaling, we inhibited Na+/Ca2+ exchange with KB-R7943, which mimicked GABA-induced Ca2+ transients. Endogenous GABA release from neurons, activated by stimulation of afferent axons or NMDA application, also triggered Ca2+ transients in astrocytes. The significance of GABAergic Ca2+ signaling in astrocytes for control of blood flow is demonstrated by SNAP 5114-sensitive constriction of blood vessels accompanying GABA uptake. The results suggest that GABAergic signaling is composed of GABA uptake-mediated Na+ rises that reduce Na+/Ca2+ exchange, thereby leading to a Ca2+ increase sufficient to trigger Ca2+-induced Ca2+ release via InsP3 receptors. Hence, GABA transporters not only remove GABA from the extracellular space, but may also contribute to intracellular signaling and astrocyte function, such as control of blood flow. [PUBLICATION ABSTRACT]
ISSN:0027-8424
1091-6490