Journal Article

DZNE-2026-00548

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png 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, K. W. ; Chalmers, N. ; Fan, J. ; Beckervordersandforth, R. ; Henneberger, C.DZNE* ; Ullah, G. ; Rose, C. R.

2026
Springer Nature [London]

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Please use a persistent id in citations: 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.

Keyword(s): Animals (MeSH) ; Astrocytes: metabolism (MeSH) ; Astrocytes: cytology (MeSH) ; Sodium: metabolism (MeSH) ; Homeostasis (MeSH) ; Sodium-Potassium-Exchanging ATPase: metabolism (MeSH) ; Sodium-Potassium-Exchanging ATPase: genetics (MeSH) ; Brain: metabolism (MeSH) ; Brain: cytology (MeSH) ; Mice (MeSH) ; Potassium: metabolism (MeSH) ; Mice, Inbred C57BL (MeSH) ; Male (MeSH) ; Sodium ; Sodium-Potassium-Exchanging ATPase ; Potassium

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Contributing Institute(s):

1. Synaptic and Glial Plasticity (AG Henneberger)

Research Program(s):

1. 351 - Brain Function (POF4-351) (POF4-351)

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