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@ARTICLE{Sarmadi:285253,
author = {Sarmadi, Kamyab and Gaspar, Linda and Bedner, Peter and
Henning, Lukas and Henneberger, Christian and Jabs, Ronald
and Jentsch, Thomas J and Steinhäuser, Christian and
Seifert, Gerald},
title = {{LRRC}8-{M}ediated {G}lutamate {R}elease from {A}strocytes
{I}s {N}ot {I}ncreased {D}uring the {I}nitiation of
{E}xperimental {T}emporal {L}obe {E}pilepsy.},
journal = {International journal of molecular sciences},
volume = {27},
number = {3},
issn = {1422-0067},
address = {Basel},
publisher = {Molecular Diversity Preservation International},
reportid = {DZNE-2026-00195},
pages = {1589},
year = {2026},
abstract = {LRRC8 channels are volume-regulated anion channels (VRACs)
activated by cellular swelling, which mediate regulatory
volume decrease in many cell types. Recently, it has been
shown that these channels contribute to the release of
glutamate from astrocytes. Since enhanced extracellular
glutamate concentrations produce hyperexcitability, and
microdialysis revealed elevated levels of the transmitter in
the brains of epileptic patients, we asked whether
astroglial glutamate release through LRRC8/VRACs might
contribute to the initiation of experimental temporal lobe
epilepsy (TLE). Patch clamp, pharmacological, and
single-cell transcript analyses were performed in the
hippocampus of controls and mice with inducible deletion of
LRRC8a in astrocytes. In addition, these mice were exposed
to our unilateral intracortical kainate model of TLE. Tonic
currents were recorded from CA1 pyramidal neurons as a
measure of glutamate release. Our data show that neither
expression of LRRC8a nor the amplitude of tonic currents was
altered 4 h after status epilepticus-induced TLE. These
findings do not suggest that increased astroglial glutamate
release through LRRC8 channels contributes to the initiation
of experimental TLE.},
keywords = {Astrocytes: metabolism / Animals / Epilepsy, Temporal Lobe:
metabolism / Epilepsy, Temporal Lobe: pathology / Glutamic
Acid: metabolism / Mice / Disease Models, Animal / Membrane
Proteins: metabolism / Membrane Proteins: genetics / Male /
Kainic Acid / Mice, Inbred C57BL / Pyramidal Cells:
metabolism / Hippocampus: metabolism / SWELL1 (Other) / VRAC
(Other) / VSOR (Other) / astrocyte (Other) / chloride
channel (Other) / epilepsy (Other) / Glutamic Acid (NLM
Chemicals) / Membrane Proteins (NLM Chemicals) / Kainic Acid
(NLM Chemicals)},
cin = {AG Henneberger},
ddc = {540},
cid = {I:(DE-2719)1013029},
pnm = {351 - Brain Function (POF4-351)},
pid = {G:(DE-HGF)POF4-351},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:41684009},
pmc = {pmc:PMC12898268},
doi = {10.3390/ijms27031589},
url = {https://pub.dzne.de/record/285253},
}