Dorso‐Ventral and Night‐Day Regulation of Extracellular K ⁺ Dynamics in Mouse Hippocampal Astrocytes
Abstract
Astrocytes regulate extracellular potassium (K + ) through multiple mechanisms operating across distinct spatiotemporal scales, yet whether this regulation exhibits regional and circadian specificity remains unclear. Using real-time K + measurements combined with electrophysiology and immunohistochemistry in astrocytes, we characterize K + buffering by astrocytes across the dorsoventral hippocampal axis at three circadian times. We report that hippocampal CA1 stratum radiatum astrocytes possess different functional K + buffering capacities depending on both anatomical location and time of day. At the early light phase (ZT3), the ventral hippocampus (VH) exhibits faster K + accumulation and greater peak amplitudes than the dorsal hippocampus (DH) in response to similar neuronal network activity. This regional divergence is driven by reduced Kir4.1 channel function in VH astrocytes, which persists across all measured time points, and which is partially compensated by enhanced Na + /K + -ATPase activity specifically at ZT3. Gap junction coupling between astrocytes shows regional and time-dependent variation, with elevated coupling in VH at ZT3 that subsequently normalizes. Kir4.1 protein expression exhibits circadian dynamics. In contrast to the steady, high levels of Kir4.1 observed in the DH, the VH shows a gradual increase in expression across the lightdark cycle. These findings establish astrocytic K + buffering as a multiscale phenomenon integrating regional heterogeneity with circadian regulation, with implications for understanding regional and temporal differences in network excitability, particularly in epilepsy.
| IntroductionUnder physiological conditions, extracellular K + concentration ([K + ] o ) fluctuates between 2 and 5 mM, while increases above 10 mM are linked to pathological activities such as seizures and spreading depression (de Curtis et al. 2018; Enger et al. 2015; Erecińska and Silver 1994). Maintaining [K + ] o within narrow physiological limits is therefore functionally important.
Astrocytes play an important role in regulating [K + ] o by taking up excess extracellular K + , redistributing it through gapjunction-connected networks, and extruding it where [K + ] o is lower (Wallraff et al. 2006; Walz 2000). This process relies on inward-rectifying Kir4.1 channels (Seifert et al. 2009), and the Na + /K + -ATPase pump. Impairment of either component can increase neuronal and network activity and excitability (Djukic et al. 2007; Romanos et al.
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BibTeX
@article{kiani2026dorsoventral,
title = {{Dorso‐Ventral and Night‐Day Regulation of Extracellular K ⁺ Dynamics in Mouse Hippocampal Astrocytes}},
author = {Nariman Kiani and Kabeer Abubakar and Tin Luka Petanjek and Monique Esclapez and Anton Ivanov and Christophe Bernard},
journal = {Glia},
year = {2026},
month = jul,
doi = {10.1002/glia.70201},
url = {https://amu.hal.science/hal-05843639v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Dorso‐Ventral and Night‐Day Regulation of Extracellular K ⁺ Dynamics in Mouse Hippocampal Astrocytes
AU - Nariman Kiani
AU - Kabeer Abubakar
AU - Tin Luka Petanjek
AU - Monique Esclapez
AU - Anton Ivanov
AU - Christophe Bernard
PY - 2026
DA - 2026/07/09
JO - Glia
DO - 10.1002/glia.70201
UR - https://amu.hal.science/hal-05843639v1
AB - Astrocytes regulate extracellular potassium (K + ) through multiple mechanisms operating across distinct spatiotemporal scales, yet whether this regulation exhibits regional and circadian specificity remains unclear. Using real-time K + measurements combined with electrophysiology and immunohistochemistry in astrocytes, we characterize K + buffering by astrocytes across the dorsoventral hippocampal axis at three circadian times. We report that hippocampal CA1 stratum radiatum astrocytes possess different functional K + buffering capacities depending on both anatomical location and time of day. At the early light phase (ZT3), the ventral hippocampus (VH) exhibits faster K + accumulation and greater peak amplitudes than the dorsal hippocampus (DH) in response to similar neuronal network activity. This regional divergence is driven by reduced Kir4.1 channel function in VH astrocytes, which persists across all measured time points, and which is partially compensated by enhanced Na + /K + -ATPase activity specifically at ZT3. Gap junction coupling between astrocytes shows regional and time-dependent variation, with elevated coupling in VH at ZT3 that subsequently normalizes. Kir4.1 protein expression exhibits circadian dynamics. In contrast to the steady, high levels of Kir4.1 observed in the DH, the VH shows a gradual increase in expression across the lightdark cycle. These findings establish astrocytic K + buffering as a multiscale phenomenon integrating regional heterogeneity with circadian regulation, with implications for understanding regional and temporal differences in network excitability, particularly in epilepsy. | IntroductionUnder physiological conditions, extracellular K + concentration ([K + ] o ) fluctuates between 2 and 5 mM, while increases above 10 mM are linked to pathological activities such as seizures and spreading depression (de Curtis et al. 2018; Enger et al. 2015; Erecińska and Silver 1994). Maintaining [K + ] o within narrow physiological limits is therefore functionally important. Astrocytes play an important role in regulating [K + ] o by taking up excess extracellular K + , redistributing it through gapjunction-connected networks, and extruding it where [K + ] o is lower (Wallraff et al. 2006; Walz 2000). This process relies on inward-rectifying Kir4.1 channels (Seifert et al. 2009), and the Na + /K + -ATPase pump. Impairment of either component can increase neuronal and network activity and excitability (Djukic et al. 2007; Romanos et al.
SN - 0894-1491
SN - 1098-1136
ER -