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Mitochondrial dysfunction and role in spreading depolarization and seizure

  • Patrick Toglia
  • Ghanim UllahEmail author
Article
  • 23 Downloads

Abstract

The effect of pathological phenomena such as epileptic seizures and spreading depolarization (SD) on mitochondria and the potential feedback of mitochondrial dysfunction into the dynamics of those phenomena are complex and difficult to study experimentally due to the simultaneous changes in many variables governing neuronal behavior. By combining a model that accounts for a wide range of neuronal behaviors including seizures, normoxic SD, and hypoxic SD (HSD), together with a detailed model of mitochondrial function and intracellular Ca2+ dynamics, we investigate mitochondrial dysfunction and its potential role in recovery of the neuron from seizures, HSD, and SD. Our results demonstrate that HSD leads to the collapse of mitochondrial membrane potential and cellular ATP levels that recover only when normal oxygen supply is restored. Mitochondrial organic phosphate and pH gradients determine the strength of the depolarization block during HSD and SD, how quickly the cell enters the depolarization block when the oxygen supply is disrupted or potassium in the bath solution is raised beyond the physiological value, and how fast the cell recovers from SD and HSD when normal potassium concentration and oxygen supply are restored. Although not as dramatic as phosphate and pH gradients, mitochondrial Ca2+ uptake has a similar effect on neuronal behavior during these conditions.

Keywords

Spreading depolarization Seizures Mitochondrial dysfunction Ion concentrations Volume dynamics Hypoxia 

Notes

Acknowledgements

This study was supported by a startup grant from Collage of Arts and Sciences awarded to Ghanim Ullah.

Compliance with Ethical Standards

Conflict of interests

The authors declare that they have no conflict of interest.

Supplementary material

10827_2019_724_MOESM1_ESM.pdf (406 kb)
(PDF 406 KB)

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of PhysicsUniversity of South FloridaTampaUSA

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