Increased membrane Ca(2+) permeability drives astrocytic Ca(2+) dynamics during 
neuronal stimulation at excitatory synapses

Hjukse, Jarand B.; Puebla, Mario F. D. L.; Vindedal, Gry Fluge; Sprengel, Rolf; Jensen, Vidar; Nagelhus, Erlend A.; Tang, Wannan

doi:10.1002/glia.24450

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Increased membrane Ca(2+) permeability drives astrocytic Ca(2+) dynamics during neuronal stimulation at excitatory synapses

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Sprengel, Rolf
Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Max Planck Society;

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Citation

Hjukse, J. B., Puebla, M. F. D. L., Vindedal, G. F., Sprengel, R., Jensen, V., Nagelhus, E. A., et al. (2023). Increased membrane Ca(2+) permeability drives astrocytic Ca(2+) dynamics during neuronal stimulation at excitatory synapses. Glia, 71(12), 2770-2781. doi:10.1002/glia.24450.

Cite as: https://hdl.handle.net/21.11116/0000-000E-2648-7

Abstract

Astrocytes are intricately involved in the activity of neural circuits; however, their basic physiology of interacting with nearby neurons is not well established. Using two-photon imaging of neurons and astrocytes during higher frequency stimulation of hippocampal CA3-CA1 Schaffer collateral (Scc) excitatory synapses, we could show that increasing levels of released glutamate accelerated local astrocytic Ca2+ elevation. However, blockage of glutamate transporters did not abolish this astrocytic Ca2+ response, suggesting that astrocytic Ca2+ elevation is indirectly associated with an uptake of extracellular glutamate. However, during the astrocytic glutamate uptake, the Na+ /Ca2+ exchanger (NCX) reverse mode was activated, and mediated extracellular Ca2+ entry, thereby triggering the internal release of Ca2+ . In addition, extracellular Ca2+ entry via membrane P2X receptors further facilitated astrocytic Ca2+ elevation via ATP binding. These findings suggest a novel mechanism of activity induced Ca2+ permeability increases of astrocytic membranes, which drives astrocytic responses during neuronal stimulation of CA3-CA1 Scc excitatory synapses.