Cellular and subcellular heterogeneity of astrocytic Na⁺ homeostasis tuning astrocytes into functionally distinct subgroups in the mouse brain

Meyer J, Bornemann V, Bhattarai A, Eitelmann S, Unichenko P, Durry S, Kafitz KW, Chalmers N, Fan J, Beckervordersandforth R, Henneberger C, Ullah G, Rose CR (2026)

Publication Type: Journal article

Publication year: 2026

Journal

Nature Communications Nature Publishing Group: Nature Communications

Book Volume: 17

Article Number: 4515

Journal Issue: 1

DOI: 10.1038/s41467-026-73435-z

Abstract

Astrocytes maintain extracellular ion and transmitter homeostasis, with the Na⁺ inward gradient playing a crucial role. Earlier studies suggested a rather low, uniform Na⁺ distribution in astrocytes, consistent with the view that these basic homeostatic properties are well-protected. Here, we employed multi-photon fluorescence lifetime imaging to quantitatively determine astrocytic [Na⁺] in mouse brain tissue slices and in vivo. Our data reveals a significant subcellular and cellular heterogeneity in astrocytic [Na⁺], accompanied by differences in the capacity for Na⁺/K⁺-ATPase (NKA)-mediated uptake of extracellular K⁺. RNAscope and immunohistochemistry indicate differential spatial expression patterns of NKA ß1 and ß2 subunits in astrocytes. Biophysical modeling of differential NKA expression together with varying strength of Na⁺ influx replicate the experimentally observed heterogeneity in astrocytic [Na⁺]. Altogether, our results suggest the existence of functionally distinct astrocytes and astrocyte subdomains in which Na⁺ homeostasis is locally adapted to the specific requirements of surrounding neural networks.

Authors with CRIS profile

Nicholas Chalmers Professur für Molekulare Medizin mit dem Schwerpunkt Molekulare Bildgebung Ruth Beckervordersandforth-Bonk Professur für Molekulare Neuropathologie (Heisenberg-Professur)

Involved external institutions

Heinrich-Heine-Universität Düsseldorf

Germany (DE) Rheinische Friedrich-Wilhelms-Universität Bonn

Germany (DE) University of South Florida (USF)

United States (USA) (US)

How to cite

APA:

Meyer, J., Bornemann, V., Bhattarai, A., Eitelmann, S., Unichenko, P., Durry, S.,... Rose, C.R. (2026). Cellular and subcellular heterogeneity of astrocytic Na⁺ homeostasis tuning astrocytes into functionally distinct subgroups in the mouse brain. Nature Communications, 17(1). https://doi.org/10.1038/s41467-026-73435-z

MLA:

Meyer, Jan, et al. "Cellular and subcellular heterogeneity of astrocytic Na⁺ homeostasis tuning astrocytes into functionally distinct subgroups in the mouse brain." Nature Communications 17.1 (2026).

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