Tyurikova, Olga;
Kopach, Olga;
Zheng, Kaiyu;
Rathore, Daman;
Codadu, Neela;
Wu, Sheng-Yi;
Shen, Yi;
... Rusakov, Dmitri A; + view all
(2025)
Astrocyte Kir4.1 expression level territorially controls excitatory transmission in the brain.
Cell Reports
, 44
(2)
, Article 115299. 10.1016/j.celrep.2025.115299.
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Abstract
Intense brain activity elevates extracellular potassium, potentially leading to overexcitation and seizures. Astrocytes are crucial for restoring healthy potassium levels, and an emerging focus on their Kir4.1 channels has reopened the quest into the underlying mechanisms. We find that the Kir4.1 level in individual astrocytes sets the kinetics of their potassium and glutamate uptake current. Combining electrophysiology with multiplexed optical sensor imaging and FLIM reveals that rises in extracellular potassium would normally boost presynaptic Ca2+ entry and release probability at excitatory synapses unless such synapses are surrounded by the Kir4.1-overexpressing astrocytes. Inside the territories of Kir4.1-overexpressing astrocytes, high-frequency afferent stimulation fails to induce long-term synaptic potentiation, and the high-potassium waves of cortical spreading depolarization are markedly attenuated. Biophysical exploration explains how astrocytes can regulate local potassium homeostasis by engaging Kir4.1 channels. Our findings thus point to a fundamental astrocytic mechanism that can restrain the activity-driven rise of excitability in brain circuits.
| Type: | Article |
|---|---|
| Title: | Astrocyte Kir4.1 expression level territorially controls excitatory transmission in the brain |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.celrep.2025.115299 |
| Publisher version: | https://doi.org/10.1016/j.celrep.2025.115299 |
| Language: | English |
| Additional information: | ©2025 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Cell Biology, STIMULUS-INDUCED RISES, RAT OPTIC-NERVE, EXTRACELLULAR POTASSIUM, SPREADING DEPRESSION, CALCIUM-CONCENTRATION, VOLTAGE-DEPENDENCE, GLUTAMATE RELEASE, K+ CHANNELS, KNOCK-OUT, IN-VIVO |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Experimental Epilepsy |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10206841 |
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