The role of extracellular potassium dynamics in the different stages of ictal bursting and spreading depression: A computational study |
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Authors: | Gerson Florence,Markus A. Dahlem,José W.M. Bassani |
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Affiliation: | a Department of Biomedical Engineering, UNICAMP, Caixa Postal 6040, 13084-971 Campinas, SP, Brazil b Laboratory of Experimental and Computational Neuroscience, Department of Biomedical Engineering, Federal University of São João del-Rei, 36.301-160 São João del-Rei, MG, Brazil c Interdisciplinary Center for Dynamics of Complex Systems, University of Potsdam, Am Neuen Palais 19, D-14415 Potsdam, Germany d Institute for Theoretical Physics, Technological University of Berlin, Hardenbergstraße 36, D-10623 Berlin, Germany e Department of Physics, Humboldt University, Newtonstraße 15, D-12489 Berlin, Germany f Potsdam Institute for Climate Impact Research, PO Box 601203, D-14412 Potsdam, Germany |
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Abstract: | Experimental evidences point out the participation of nonsynaptic mechanisms (e.g., fluctuations in extracellular ions) in epileptiform bursting and spreading depression (SD). During these abnormal oscillatory patterns, it is observed an increase of extracellular potassium concentration [K+]o and a decrease of extracellular calcium concentration [Ca2+]o which raises the neuronal excitability. However, whether the high [K+]o triggers and propagates these abnormal neuronal activities or plays a secondary role into this process is unclear. To better understand the influence of extracellular potassium dynamics in these oscillatory patterns, the experimental conditions of high [K+]o and zero [Ca2+]o were replicated in an extended Golomb model where we added important regulatory mechanisms of ion concentration as Na+-K+ pump, ion diffusion and glial buffering. Within these conditions, simulations of the cell model exhibit seizure-like discharges (ictal bursting). The SD was elicited by the interruption of the Na+−K+ pump activity, mimicking the effect of cellular hypoxia (an experimental protocol to elicit SD, the hypoxia-induced SD). We used the bifurcation theory and the fast-slow method to analyze the interference of K+ dynamics in the cellular excitability. This analysis indicates that the system loses its stability at a high [K+]o, transiting to an elevated state of neuronal excitability. Effects of high [K+]o are observed in different stages of ictal bursting and SD. In the initial stage, the increase of [K+]o creates favorable conditions to trigger both oscillatory patterns. During the neuronal activity, a continuous growth of [K+]o by outward K+ flow depresses K+ currents in a positive feedback way. At the last stage, due to the depression of K+ currents, the Na+-K+ pump is the main mechanism in the end of neuronal activity. Thus, this work suggests that [K+]o dynamics may play a fundamental role in these abnormal oscillatory patterns. |
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Keywords: | Extracellular potassium concentration Excitability Bifurcation Ictal bursting Spreading depression |
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