Astrocytic Ion Dynamics: Implications for Potassium Buffering and Liquid Flow

Halnes, Geir; Pettersen, Klas H.; Øyehaug, Leiv; Rognes, Marie E.; Einevoll, Gaute T.

doi:10.1007/978-3-030-00817-8_14

Cited by 13 publications

(16 citation statements)

References 89 publications

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“…To calculate the osmotically induced volume changes dV/dt, we used the formalism outlined in [51]. The water flow Q across the membrane is given by…”

Section: Volume Dynamicsmentioning

confidence: 99%

“…Furthermore, when ion concentrations change in neurons, astrocytes, and the ECS, it will cause osmotic pressure gradients over the cellular membrane. This can lead to cellular swelling or shrinkage [48][49][50][51], which in turn will alter the ionic concentrations in the swollen or shrunken volumes. Cellular swelling and a corresponding shrinkage of the ECS is, for example, an important trademark of pathological conditions such as seizures and spreading depression [52][53][54].…”

Section: Introductionmentioning

confidence: 99%

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An electrodiffusive neuron-extracellular-glia model for exploring the genesis of slow potentials in the brain

2021

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Within the computational neuroscience community, there has been a focus on simulating the electrical activity of neurons, while other components of brain tissue, such as glia cells and the extracellular space, are often neglected. Standard models of extracellular potentials are based on a combination of multicompartmental models describing neural electrodynamics and volume conductor theory. Such models cannot be used to simulate the slow components of extracellular potentials, which depend on ion concentration dynamics, and the effect that this has on extracellular diffusion potentials and glial buffering currents. We here present the electrodiffusive neuron-extracellular-glia (edNEG) model, which we believe is the first model to combine compartmental neuron modeling with an electrodiffusive framework for intra- and extracellular ion concentration dynamics in a local piece of neuro-glial brain tissue. The edNEG model (i) keeps track of all intraneuronal, intraglial, and extracellular ion concentrations and electrical potentials, (ii) accounts for action potentials and dendritic calcium spikes in neurons, (iii) contains a neuronal and glial homeostatic machinery that gives physiologically realistic ion concentration dynamics, (iv) accounts for electrodiffusive transmembrane, intracellular, and extracellular ionic movements, and (v) accounts for glial and neuronal swelling caused by osmotic transmembrane pressure gradients. The edNEG model accounts for the concentration-dependent effects on ECS potentials that the standard models neglect. Using the edNEG model, we analyze these effects by splitting the extracellular potential into three components: one due to neural sink/source configurations, one due to glial sink/source configurations, and one due to extracellular diffusive currents. Through a series of simulations, we analyze the roles played by the various components and how they interact in generating the total slow potential. We conclude that the three components are of comparable magnitude and that the stimulus conditions determine which of the components that dominate.

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“…To calculate the osmotically induced volume changes dV/dt, we used the formalism outlined in [51]. The water flow Q across the membrane is given by…”

Section: Volume Dynamicsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

An electrodiffusive neuron-extracellular-glia model for exploring the genesis of slow potentials in the brain

2021

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Section: Introductionmentioning

confidence: 99%

An electrodiffusive neuron-extracellular-glia model with somatodendritic interactions

Sætra

Einevoll

Halnes

2020

Preprint

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Computational modeling in neuroscience has largely focused on simulating the electrical activity of neurons, while ignoring other components of brain tissue, such as glial cells and the extracellular space. As such, most existing models can not be used to address pathological conditions, such as spreading depression, which involves dramatic changes in ion concentrations, large extracellular potential gradients, and glial buffering processes. We here present the electrodiffusive neuron-extracellular-glia (edNEG) model, which we believe is the first model to combine multicompartmental neuron modeling with an electrodiffusive framework for intra- and extracellular ion concentration dynamics in a local piece of neuro-glial brain tissue. The edNEG model (i) keeps track of all intraneuronal, intraglial, and extracellular ion concentrations and electrical potentials, (ii) accounts for neuronal somatic action potentials, and dendritic calcium spikes, (iii) contains a neuronal and glial homeostatic machinery that gives physiologically realistic ion concentration dynamics, (iv) accounts for electrodiffusive transmembrane, intracellular, and extracellular ionic movements, and (v) accounts for glial and neuronal swelling caused by osmotic transmembrane pressure gradients. We demonstrate that the edNEG model performs realistically as a local and closed system, i.e., that it maintains a steady state for moderate neural activity, but experiences concentration-dependent effects, such as altered firing patterns and homeostatic breakdown, when the activity level becomes too intense. Furthermore, we study the role of glia in making the neuron more tolerable to hyperactive firing and in limiting neuronal swelling. Finally, we discuss how the edNEG model can be integrated with previous spatial continuum models of spreading depression to account for effects of neuronal morphology, action potential generation, and dendritic Ca2+ spikes which are currently not included in these models.Author summaryNeurons communicate by electrical signals mediated by the movement of ions across the cell membranes. The ionic flow changes the ion concentrations on both sides of the cell membranes, but most modelers of neurons assume ion concentrations to remain constant. Since the neuronal membrane contains structures called ion pumps and cotransporters that work to maintain close-to baseline ion concentrations, and the brain contains a cell type called astrocytes that contribute in keeping an appropriate ionic environment for neurons, the assumption is justifiable in many scenarios. However, for several pathological conditions, such as epilepsy and spreading depression, the ion concentrations may vary dramatically. To study these scenarios, we need models that account for changes in ion concentrations. In this paper, we present what we call the electrodiffusive neuron-extracellular-glia model (edNEG), which keeps track of all ions in a closed system containing a neuron, the extracellular space surrounding it, and an astrocytic “domain”. The edNEG model ensures a complete and consistent relationship between ion concentrations and charge conservation. We envision that the model can be used to study a range of pathological conditions such as spreading depression and, hence, be of great value for the field of neuroscience.

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“…In addition, ionic diffusion between astrocytes is mediated by gap junction channels, which create narrow passages, leading to a Poissonian law for the exchange rate (Holcman and Schuss, 2013). Such local description emphasizes the global electrodiffusion here simulated during either dynamical changes induced by neuronal activity or during subsequent steady states (Ostby et al, 2009;Oyehaug et al, 2012;Halnes et al, 2013;Halnes et al, 2016). Osmotic pressures and aquaporin4 (AQ4) water based fluxes are also simulated and are proposed to account for changes in both astrocytic swelling and ECS volume.…”

Section: Computational Modeling Of Astroglial Regulation Of Extracellmentioning

confidence: 97%

“…Such approach showed that astrocytes can control extracellular levels of K + and glutamate solely during mild ischemia. Interestingly, more recent modeling studies on astrocyte ion dynamics and implications of spatial K + buffering put forward a multiscale theory that includes not only local ionic exchanges and diffusive processes, but also osmotic changes and volume regulations (Ostby et al, 2009;Oyehaug et al, 2012;Halnes et al, 2013;Halnes et al, 2016). This model indeed proposes that astroglial ion dynamics might modulate microscopic liquid flow via osmotic effects resulting in whole-brain macroscopic flow.…”

Section: Computational Modeling Of Astroglial Regulation Of Extracellmentioning

confidence: 99%

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

Rouach

Duc

Sibille

et al. 2018

Preprint

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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 K ir 4.1 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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Astrocytic Ion Dynamics: Implications for Potassium Buffering and Liquid Flow

Cited by 13 publications

References 89 publications

An electrodiffusive neuron-extracellular-glia model for exploring the genesis of slow potentials in the brain

An electrodiffusive neuron-extracellular-glia model for exploring the genesis of slow potentials in the brain

An electrodiffusive neuron-extracellular-glia model with somatodendritic interactions

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

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