TY  - JOUR
AU  - Sarmadi, Kamyab
AU  - Gaspar, Linda
AU  - Bedner, Peter
AU  - Henning, Lukas
AU  - Henneberger, Christian
AU  - Jabs, Ronald
AU  - Jentsch, Thomas J
AU  - Steinhäuser, Christian
AU  - Seifert, Gerald
TI  - LRRC8-Mediated Glutamate Release from Astrocytes Is Not Increased During the Initiation of Experimental Temporal Lobe Epilepsy.
JO  - International journal of molecular sciences
VL  - 27
IS  - 3
SN  - 1422-0067
CY  - Basel
PB  - Molecular Diversity Preservation International
M1  - DZNE-2026-00195
SP  - 1589
PY  - 2026
AB  - 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.
KW  - Astrocytes: metabolism
KW  - Animals
KW  - Epilepsy, Temporal Lobe: metabolism
KW  - Epilepsy, Temporal Lobe: pathology
KW  - Glutamic Acid: metabolism
KW  - Mice
KW  - Disease Models, Animal
KW  - Membrane Proteins: metabolism
KW  - Membrane Proteins: genetics
KW  - Male
KW  - Kainic Acid
KW  - Mice, Inbred C57BL
KW  - Pyramidal Cells: metabolism
KW  - Hippocampus: metabolism
KW  - SWELL1 (Other)
KW  - VRAC (Other)
KW  - VSOR (Other)
KW  - astrocyte (Other)
KW  - chloride channel (Other)
KW  - epilepsy (Other)
KW  - Glutamic Acid (NLM Chemicals)
KW  - Membrane Proteins (NLM Chemicals)
KW  - Kainic Acid (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:41684009
C2  - pmc:PMC12898268
DO  - DOI:10.3390/ijms27031589
UR  - https://pub.dzne.de/record/285253
ER  -