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@ARTICLE{Untiet:823823,
author = {Untiet, Verena and Kovermann, Peter and Gerkau, Niklas J.
and Gensch, Thomas and Rose, Christine R. and Fahlke,
Christoph},
title = {{G}lutamate transporter-associated anion channels adjust
intracellular chloride concentrations during glial
maturation},
journal = {Glia},
volume = {65},
number = {2},
issn = {0894-1491},
address = {Bognor Regis [u.a.]},
publisher = {Wiley-Liss},
reportid = {FZJ-2016-06463},
pages = {388–400},
year = {2017},
abstract = {Astrocytic volume regulation and neurotransmitter uptake
are critically dependent on the intracellular anion
concentration, but little is known about the mechanisms
controlling internal anion homeostasis in these cells. Here
we used fluorescence lifetime imaging microscopy (FLIM) with
the chloride-sensitive dye MQAE to measure intracellular
chloride concentrations in murine Bergmann glial cells in
acute cerebellar slices. We found Bergmann glial [Cl−]int
to be controlled by two opposing transport processes:
chloride is actively accumulated by the Na+-K+-2Cl−
cotransporter NKCC1, and chloride efflux through anion
channels associated with excitatory amino acid transporters
(EAATs) reduces [Cl−]int to values that vary upon changes
in expression levels or activity of these channels. EAATs
transiently form anion-selective channels during glutamate
transport, and thus represent a class of ligand-gated anion
channels. Age-dependent upregulation of EAATs results in a
developmental chloride switch from high internal chloride
concentrations (51.6 ± 2.2 mM, $mean ± 95\%$
confidence interval) during early development to adult
levels (35.3 ± 0.3 mM). Simultaneous blockade of
EAAT1/GLAST and EAAT2/GLT-1 increased [Cl−]int in adult
glia to neonatal values. Moreover, EAAT activation by
synaptic stimulations rapidly decreased [Cl−]int. Other
tested chloride channels or chloride transporters do not
contribute to [Cl−]int under our experimental conditions.
Neither genetic removal of ClC-2 nor pharmacological block
of K+-Cl− cotransporter change resting Bergmann glial
[Cl−]int in acute cerebellar slices. We conclude that EAAT
anion channels play an important and unexpected role in
adjusting glial intracellular anion concentration during
maturation and in response to cerebellar activity.},
cin = {ICS-4},
ddc = {610},
cid = {I:(DE-Juel1)ICS-4-20110106},
pnm = {553 - Physical Basis of Diseases (POF3-553)},
pid = {G:(DE-HGF)POF3-553},
typ = {PUB:(DE-HGF)16},
UT = {WOS:000393669100012},
pubmed = {pmid:27859594},
doi = {10.1002/glia.23098},
url = {https://juser.fz-juelich.de/record/823823},
}