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

## TL;DR

This study investigates whether glutamate release from astrocytes via LRRC8 channels contributes to the start of temporal lobe epilepsy but finds no evidence supporting this.

## Contribution

The study provides new evidence that LRRC8-mediated glutamate release does not play a role in initiating experimental temporal lobe epilepsy.

## Key findings

- Expression of LRRC8a in astrocytes was not altered after the onset of experimental TLE.
- Tonic glutamate currents in pyramidal neurons were unchanged following TLE induction.
- Results suggest LRRC8 channels do not contribute to glutamate release during TLE initiation.

## 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.