LRRC8-Mediated Glutamate Release from Astrocytes Is Not Increased During the Initiation of Experimental Temporal Lobe Epilepsy

Sarmadi, Kamyab; Gaspar, Linda; Bedner, Peter; Henning, Lukas; Henneberger, Christian; Jabs, Ronald; Jentsch, Thomas J.; Steinhäuser, Christian; Seifert, Gerald

doi:10.3390/ijms27031589

This is an early access version, the complete PDF, HTML, and XML versions will be available soon.

Open AccessArticle

LRRC8-Mediated Glutamate Release from Astrocytes Is Not Increased During the Initiation of Experimental Temporal Lobe Epilepsy

by

Kamyab Sarmadi

^1,†,

Linda Gaspar

^1,†,

Peter Bedner

¹

,

Lukas Henning

^1,‡

,

Christian Henneberger

^1,2

,

Ronald Jabs

¹

,

Thomas J. Jentsch

^3,4

,

Christian Steinhäuser

^1,*

and

Gerald Seifert

^1,*

¹

Institute of Cellular Neurosciences I, University Hospital Bonn, University of Bonn, 53127 Bonn, Germany

²

German Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany

³

Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), 13125 Berlin, Germany

⁴

NeuroCure Cluster of Excellence, Charité Universitätsmedizin Berlin, 10117 Berlin, Germany

^*

Authors to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

^‡

Current address: Department of Epileptology, University Hospital Bonn, 53127 Bonn, Germany.

Int. J. Mol. Sci. 2026, 27(3), 1589; https://doi.org/10.3390/ijms27031589

Submission received: 17 December 2025 / Revised: 29 January 2026 / Accepted: 3 February 2026 / Published: 5 February 2026

(This article belongs to the Special Issue Role of Glia in Human Health and Disease)

Download

Browse Figure

Versions Notes

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: VRAC; VSOR; SWELL1; chloride channel; astrocyte; epilepsy

Graphical Abstract

Share and Cite

MDPI and ACS Style

Sarmadi, K.; Gaspar, L.; Bedner, P.; Henning, L.; Henneberger, C.; Jabs, R.; Jentsch, T.J.; Steinhäuser, C.; Seifert, G. LRRC8-Mediated Glutamate Release from Astrocytes Is Not Increased During the Initiation of Experimental Temporal Lobe Epilepsy. Int. J. Mol. Sci. 2026, 27, 1589. https://doi.org/10.3390/ijms27031589

AMA Style

Sarmadi K, Gaspar L, Bedner P, Henning L, Henneberger C, Jabs R, Jentsch TJ, Steinhäuser C, Seifert G. LRRC8-Mediated Glutamate Release from Astrocytes Is Not Increased During the Initiation of Experimental Temporal Lobe Epilepsy. International Journal of Molecular Sciences. 2026; 27(3):1589. https://doi.org/10.3390/ijms27031589

Chicago/Turabian Style

Sarmadi, Kamyab, Linda Gaspar, Peter Bedner, Lukas Henning, Christian Henneberger, Ronald Jabs, Thomas J. Jentsch, Christian Steinhäuser, and Gerald Seifert. 2026. "LRRC8-Mediated Glutamate Release from Astrocytes Is Not Increased During the Initiation of Experimental Temporal Lobe Epilepsy" International Journal of Molecular Sciences 27, no. 3: 1589. https://doi.org/10.3390/ijms27031589

APA Style

Sarmadi, K., Gaspar, L., Bedner, P., Henning, L., Henneberger, C., Jabs, R., Jentsch, T. J., Steinhäuser, C., & Seifert, G. (2026). LRRC8-Mediated Glutamate Release from Astrocytes Is Not Increased During the Initiation of Experimental Temporal Lobe Epilepsy. International Journal of Molecular Sciences, 27(3), 1589. https://doi.org/10.3390/ijms27031589

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Article metric data becomes available approximately 24 hours after publication online.

Article Menu

LRRC8-Mediated Glutamate Release from Astrocytes Is Not Increased During the Initiation of Experimental Temporal Lobe Epilepsy

Abstract

Share and Cite

Article Metrics

Further Information

Guidelines

MDPI Initiatives

Follow MDPI