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Translating from Na\(^+\) to Ca\(^{2+}\): Na/Ca-exchanger exerts Na\(^+\)-dependent control over astrocytic Ca\(^{2+}\) oscillations

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Abstract

Recently accumulated evidences suggest that astrocyte signaling is in touch link with extracellular volume regulation and interstitial fluid drainage from the brain. Classical understanding of astrocyte activity is based on IP\(_3\)-dependent calcium exchange with intracellular stores. Recent evidence shifts focus to calcium entry from extracellular space via multiple mechanisms and widens it to taking other ions into account. It has been hypothesized that Na/Ca-exchanger can translate activity-dependent Na\(^+\) transients into modulation of Ca\(^{2+}\) dynamics. We combine a model of IP\(_3\)-based Ca\(^{2+}\) dynamics with a model of Ca\(^{2+}\) flow through Na/Ca-exchanger to provide theoretical insights into the possible effects of such modulation. We find that the exchanger can provide for bidirectional Na\(^+\)-dependent modulation of the sensitivity to extracellular glutamate, oscillation amplitude and frequency modulation, as well as extending the available set of dynamical regimes. The extent of the emergent Na\(^+\) sensitivity is predicted to be scaled by a morphology-dependent balance between the maximal flow through the exchanger and the rate of entry from intracellular stores.

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Acknowledgements

Yu.V. and D.V.V. acknowledge support from Russian Science Foundation, project #19-15-00201 (code writing, numeric simulation, study and discussion of Glu-driven effects). D.E.P. and A.R.B. acknowledge the support by the RFBR grant #19-515-55016 (model development, study and discussion of allosteric regulation effects).

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Authors and Affiliations

  1. Department of Theoretical Physics, Kursk State University, Radishcheva st., 33, 305000, Kursk, Russia

    Andrey Yu. Verisokin & Darya V. Verveyko

  2. Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Leninskie Gory, 1/73, Moscow, Russia

    Varvara V. Kucherenko

  3. Saratov State National Research University, Astrakhanskaya st., 83, Saratov, Russia

    Dmitry E. Postnov

  4. Biological Faculty, Lomonosov Moscow State University, Leninskie Gory, 1/24, Moscow, Russia

    Alexey R. Brazhe

  5. Department of Molecular Neurobiology, Institute of Bioorganic Chemistry RAS, Miklukho-Maklay st., 16/10, Moscow, Russia

    Alexey R. Brazhe

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  1. Andrey Yu. Verisokin
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Correspondence to Andrey Yu. Verisokin.

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Verisokin, A.Y., Verveyko, D.V., Kucherenko, V.V. et al. Translating from Na\(^+\) to Ca\(^{2+}\): Na/Ca-exchanger exerts Na\(^+\)-dependent control over astrocytic Ca\(^{2+}\) oscillations. Eur. Phys. J. Plus 136, 718 (2021). https://doi.org/10.1140/epjp/s13360-021-01687-3

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