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

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 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.

A Call to Action Toward Optimizing the Electrical Dose Received by Neural Targets in Spinal Cord Stimulation Therapy for Neuropathic Pain

“…Every 20 seconds, 32 mm is treated in this manner. The choice of a 5-second activation time was based on in vitro studies of astrocyte-depolarization times during external electrical stimulation, 50 and this fits within the framework of focusing on glial cell dynamics as part of the overall stimulation paradigm. Built within this programming paradigm is the duty cycling concept such that no region of the cord is exposed to >5 seconds of stimulation every 20 seconds.…”

Microscale physiological events on the human cortical surface

“…This could include Cajal-Retzius cells or other relatively rare cell types whose cell bodies are found in upper cortical layers (Rakic and Zecevic 2003;Mohan et al 2015;Gabbott 2016). Alternatively, these events could reflect ionic flux in glial cells in upper cortical layersalthough the fast kinetics make this somewhat less likely as astrocytic waves normally occur on the time scale of seconds (Hassinger et al 1996;Scemes and Giaume 2006;Takata and Hirase 2008;Kuga et al 2011;Khakh and McCarthy 2015;Rouach et al 2018).…”

Structural analysis of fluid flow in complex biological systems

“…Potassium accumulation and flow in the extracellular space have been shown to have important roles in aging, Alzheimer's disease, anesthesia, dementia, diabetes, epilepsy, migraine, sleep, stroke, and traumatic brain injury, as well as an important role in the biology of the central nervous system. 47,49,50,52,53,55,56,100,101,[343][344][345][346][347][348][349][350][351][352][353][354][355][356][357][358][359][360][361][362] Indeed, Filipidis et al 363 have identified many such systems in biology containing three intercalated sets of tissues, including pleura, peritoneum, pericardium, fetal membranes, and leptomeninges citing the significant references. Each of these tissues likely include intercalated syncytia and thus require multidomain models of the type we have studied.…”