Sodium Fluctuations in Astroglia and Their Potential Impact on Astrocyte Function
Open accessAbstract
Astrocytes are the main cell type responsible for the regulation of brain homeostasis, including the maintenance of ion gradients and neurotransmitter clearance. These processes are tightly coupled to changes in the intracellular sodium (Na+) concentration. While activation of the sodium-potassium-ATPase (NKA) in response to an elevation of extracellular K+ may decrease intracellular Na+, the co-transport of transmitters such as glutamate together with Na+ results in an increase in astrocytic Na+. This increase in intracellular Na+ can modulate, for instance, metabolic downstream pathways. Thereby, astrocytes are capable to react on a fast time scale to surrounding neuronal activity via intracellular Na+ fluctuations, and adjust energy production to the demand of their environment. Besides the well-documented conventional roles of Na+ signaling mainly mediated through changes in its electrochemical gradient, several recent studies have identified more atypical roles for Na+, including protein interactions leading to changes in their biochemical activity or Na+-dependent regulation of gene expression. In this review, we will address both the conventional as well as the atypical functions of astrocytic Na+ signaling, presenting the role of transporters and channels involved and their implications for physiological processes in the CNS. We will also discuss how these important functions are affected under pathological conditions including stroke and migraine. We postulate that Na+ is an essential player not only in the maintenance of homeostatic processes, but also as a messenger for the fast communication between neurons and astrocytes, adjusting the functional properties of various cellular interaction partners to the needs of the surrounding network.
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Astrocytes and the vasculature may not only respond passively to neuronal activity but may also exhibit dynamics that precede changes in neuronal network states.
“Together, these findings suggest that astrocytes and the vasculature may not only respond passively to neuronal activity but may also exhibit dynamics that precede changes in neuronal network states39,53–55.”
From Energy paradox in REM sleep: balancing supply and consumption in brain metabolism (2026) · cites this paper as [53]
The “Spontaneous Na+ Fluctuations” section (page unavailable) says astrocytes can communicate within their own network independently of neurons, supporting the point that they do more than passively respond to neuronal activity. It does not establish that astrocyte dynamics precede changes in neuronal network states, and the passages do not address preceding vascular dynamics. (LLM, conf=0.86)
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Rasmussen, M. K., Mestre, H., & Nedergaard, M. (2021) · Physiological Reviews · doi:10.1152/physrev.00031.2020 · Cited by 622 · see citing works
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- Authors
- Felix, L., Delekate, A., Petzold, G. C., & Rose, C. R.
- Affiliations
- Heinrich Heine University Düsseldorf (DE)
- German Center for Neurodegenerative Diseases (DE)
- University Hospital Bonn (DE)
- Corresponding author
- Petzold, Gabor C.
- Rose, Christine R.
- Venue
- Frontiers in Physiology
- Publisher
- Frontiers Media SA
- Published
- 2020-08-12
- Volume
- 11
- Pages
- 871-871
- ISSN
- 1664-042X (ISSN-L)
- PMC
- PMC7435049
- OpenAlex
- W3048466223
- Cited by
- 38
- References
- 221
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 4 · 2023: 9 · 2022: 7 · 2021: 9
- FWCI
- 0.86
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Physiology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- DZNE Pub (submittedVersion, other-oa)
- Funders
- German Center for Neurodegenerative Diseases
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Keywords
- astrocytes, intracellular sodium, Na+/K+-ATPase, sodium transporters, ion channels, astrocyte-neuron communication, brain homeostasis, stroke, migraine, energy metabolism
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