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Potassium and sodium microdomains in thin astroglial processes: A computational model study
- Source :
- PLoS Computational Biology, Vol 14, Iss 5, p e1006151 (2018), PLoS Computational Biology, Breslin, K, Wade, J J, Wong-lin, K, Harkin, J, Flanagan, B, Van Zalinge, H, Hall, S, Walker, M, Verkhratsky, A, Mcdaid, L & Jolivet, R B (ed.) 2018, ' Potassium and sodium microdomains in thin astroglial processes: A computational model study ', PLoS computational biology, vol. 14, no. 5 . https://doi.org/10.1371/journal.pcbi.1006151
- Publication Year :
- 2018
- Publisher :
- Public Library of Science (PLoS), 2018.
-
Abstract
- A biophysical model that captures molecular homeostatic control of ions at the perisynaptic cradle (PsC) is of fundamental importance for understanding the interplay between astroglial and neuronal compartments. In this paper, we develop a multi-compartmental mathematical model which proposes a novel mechanism whereby the flow of cations in thin processes is restricted due to negatively charged membrane lipids which result in the formation of deep potential wells near the dipole heads. These wells restrict the flow of cations to “hopping” between adjacent wells as they transverse the process, and this surface retention of cations will be shown to give rise to the formation of potassium (K+) and sodium (Na+) microdomains at the PsC. We further propose that a K+ microdomain formed at the PsC, provides the driving force for the return of K+ to the extracellular space for uptake by the neurone, thereby preventing K+ undershoot. A slow decay of Na+ was also observed in our simulation after a period of glutamate stimulation which is in strong agreement with experimental observations. The pathological implications of microdomain formation during neuronal excitation are also discussed.<br />Author summary During periods of neuronal activity, ionic homeostasis in the surrounding extracellular space (ECS) is disturbed. To provide a healthy environment for continued neuronal function, excess ions such as potassium must be buffered away from the ECS; a vital supportive role provided by astrocyte cells. It has long been thought that astrocytes not only removed ions from the ECS but also transport them to other areas of the brain where their concentrations are lower. However, while our computational model simulations agree that astrocytes do remove these ions from the ECS they also show that these ions are mainly stored locally at the PsC to be returned to the ECS, thus restoring ionic homeostasis. Furthermore, we detail in this paper that this happens because of a previously overlooked biophysical phenomenon that is only dominant in thin astrocyte processes. The flow of these cations within thin processes is primarily by surface conduction where they experience the attraction of fixed negative charge at the membrane inner surface. This negative charge constrains cation movement along the surface and so their flow rate is restricted. Consequently, ions such as potassium that are released during neuronal excitation enter the PsC and are stored locally due to the low conductance pathway between the PsC and the astrocyte soma. Our simulations also show that this local build-up of K+ is returned to the ECS after the neuronal activity dies off which could potentially explain why K+ undershoot has not been observed; this result agrees with experimental observations. Moreover, the same mechanism can also explain the transient behaviour of Na+ ions whereby in thin processes a slow decay time constant is experimentally observed. These findings have important implications for the role of astrocytes in regulating neuronal excitability under physiological and pathological conditions, and therefore highlight the significance of the work presented in this paper.
- Subjects :
- 0301 basic medicine
Macroglial Cells
Physiology
Potassium
Biochemistry
Physical Chemistry
Nervous System
0302 clinical medicine
Animal Cells
Medicine and Health Sciences
lcsh:QH301-705.5
Membrane potential
Neurons
Ecology
Neurochemistry
Neurotransmitters
Electrophysiology
Chemistry
Computational Theory and Mathematics
Modeling and Simulation
Physical Sciences
Cellular Types
Glutamate
Anatomy
Research Article
Chemical Elements
Sodium
Membrane lipids
Models, Neurological
chemistry.chemical_element
Glutamic Acid
Neurophysiology
Glial Cells
Models, Biological
Membrane Potential
Ion
03 medical and health sciences
Cellular and Molecular Neuroscience
Cations
Genetics
Extracellular
Animals
Computer Simulation
Molecular Biology
Ecology, Evolution, Behavior and Systematics
Ions
Lipid microdomain
Computational Biology
Biology and Life Sciences
Cell Biology
Dipole
030104 developmental biology
chemistry
lcsh:Biology (General)
Astrocytes
Cellular Neuroscience
Synapses
Biophysics
Extracellular Space
030217 neurology & neurosurgery
Neuroscience
Subjects
Details
- Language :
- English
- ISSN :
- 15537358
- Volume :
- 14
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- PLoS Computational Biology
- Accession number :
- edsair.doi.dedup.....b0e733c00935f9476ec01c4692d3ee3c