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Changes of Ionic Concentrations During Seizure Transitions — A Modeling Study

Damiano Gentiletti

Department of Biomedical Physics, Faculty of Physics, University of Warsaw, ul. Pasteura 5, Warsaw, Poland

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Piotr Suffczynski

Department of Biomedical Physics, Faculty of Physics, University of Warsaw, ul. Pasteura 5, Warsaw, Poland

E-mail Address: Piotr.Suffczynski@fuw.edu.pl

Corresponding author.

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Vadym Gnatkovsky

Unit of Epileptology and Experimental Neurophysiology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Via Giovanni Celoria 11, Milan, Italy

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, and

Marco de Curtis

Unit of Epileptology and Experimental Neurophysiology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Via Giovanni Celoria 11, Milan, Italy

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https://doi.org/10.1142/S0129065717500046Cited by:18 (Source: Crossref)

Abstract

Traditionally, it is considered that neuronal synchronization in epilepsy is caused by a chain reaction of synaptic excitation. However, it has been shown that synchronous epileptiform activity may also arise without synaptic transmission. In order to investigate the respective roles of synaptic interactions and nonsynaptic mechanisms in seizure transitions, we developed a computational model of hippocampal cells, involving the extracellular space, realistic dynamics of ${Na}^{+}$ ${Na}^{+}$ , $K^{+}$ $K^{+}$ , ${Ca}^{2 +}$ ${Ca}^{2 +}$ and ${Cl}^{-}$ ${Cl}^{-}$ ions, glial uptake and extracellular diffusion mechanisms. We show that the network behavior with fixed ionic concentrations may be quite different from the neurons’ behavior when more detailed modeling of ionic dynamics is included. In particular, we show that in the extended model strong discharge of inhibitory interneurons may result in long lasting accumulation of extracellular $K^{+}$ $K^{+}$ , which sustains the depolarization of the principal cells and causes their pathological discharges. This effect is not present in a reduced, purely synaptic network. These results point to the importance of nonsynaptic mechanisms in the transition to seizure.

Keywords:

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