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Dynamics of ion fluxes between neurons, astrocytes and the extracellular space during neurotransmission

Nathalie Rouach, Khanh Dao Duc, Jeremie Sibille, David Holcman
doi: https://doi.org/10.1101/305706
Nathalie Rouach
College-de-France;
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Khanh Dao Duc
UC Berkeley;
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Jeremie Sibille
Charite, Berlin;
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David Holcman
ENS
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  • For correspondence: david.holcman@ens.fr
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Abstract

Ionic homeostasis in the brain involves redistribution of ionic fluxes in several cell types and compartments, including neurons, astrocytes and the extracellular space. How the major ionic activity-dependent fluxes of potassium and sodium are individually regulated remains difficult to dissociate and to track experimentally. We here review recent progress in modeling the ionic fluxes evoked by neuronal activity based on mass conservation. Excitability of neurons indeed relies on inward sodium and outward potassium fluxes during action potential firing. Recently, we have developed a tri-compartment model based on mass-action kinetics equations that account for potassium dynamics between neurons, astrocytes and the extracellular space. This review describes how such type of model can be used to spatially and temporally predict potassium fluxes during various regimes of neuronal activity. In particular, the model initially showed that it takes several seconds for astrocytes to buffer the majority of the potassium rapidly released by neurons in both basal and high regime of activity. Such model can also probe the selective contribution of ionic channels, and revealed for instance that disruption of the main astroglial potassium Kir4.1 channels not only favors the emergence of epileptiform activity, but also dysregulates neuronal excitability specifically during slow rhythmic activities. We here also extend the predictions of the model by assessing the selective contribution of the astroglial and neuronal Na/K ATPase, or volume of the extracellular space on potassium dynamics. We discuss these findings and their implications for neuronal information processing in the healthy and diseased brain.

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Posted April 20, 2018.
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Dynamics of ion fluxes between neurons, astrocytes and the extracellular space during neurotransmission
Nathalie Rouach, Khanh Dao Duc, Jeremie Sibille, David Holcman
bioRxiv 305706; doi: https://doi.org/10.1101/305706
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Dynamics of ion fluxes between neurons, astrocytes and the extracellular space during neurotransmission
Nathalie Rouach, Khanh Dao Duc, Jeremie Sibille, David Holcman
bioRxiv 305706; doi: https://doi.org/10.1101/305706

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