Journal Article

DZNE-2020-06499

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Disentangling astroglial physiology with a realistic cell model in silico.

Savtchenko, L. P. (Corresponding author) ; Bard, L. ; Jensen, T. P. ; Reynolds, J. P. ; Kraev, I. ; Medvedev, N. ; Stewart, M. G. ; Henneberger, C.DZNE* ; Rusakov, D. A.

2018
Nature Publishing Group UK [London]

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Please use a persistent id in citations: doi:10.1038/s41467-018-05896-w

Abstract: Electrically non-excitable astroglia take up neurotransmitters, buffer extracellular K+ and generate Ca2+ signals that release molecular regulators of neural circuitry. The underlying machinery remains enigmatic, mainly because the sponge-like astrocyte morphology has been difficult to access experimentally or explore theoretically. Here, we systematically incorporate multi-scale, tri-dimensional astroglial architecture into a realistic multi-compartmental cell model, which we constrain by empirical tests and integrate into the NEURON computational biophysical environment. This approach is implemented as a flexible astrocyte-model builder ASTRO. As a proof-of-concept, we explore an in silico astrocyte to evaluate basic cell physiology features inaccessible experimentally. Our simulations suggest that currents generated by glutamate transporters or K+ channels have negligible distant effects on membrane voltage and that individual astrocytes can successfully handle extracellular K+ hotspots. We show how intracellular Ca2+ buffers affect Ca2+ waves and why the classical Ca2+ sparks-and-puffs mechanism is theoretically compatible with common readouts of astroglial Ca2+ imaging.

Keyword(s): Algorithms (MeSH) ; Amino Acid Transport System X-AG: metabolism (MeSH) ; Animals (MeSH) ; Astrocytes: metabolism (MeSH) ; Astrocytes: physiology (MeSH) ; Calcium: metabolism (MeSH) ; Computer Simulation (MeSH) ; Hippocampus: cytology (MeSH) ; Membrane Potentials (MeSH) ; Models, Neurological (MeSH) ; Neurons: metabolism (MeSH) ; Patch-Clamp Techniques (MeSH) ; Potassium Channels: metabolism (MeSH) ; Proof of Concept Study (MeSH) ; Rats (MeSH) ; Software (MeSH) ; Amino Acid Transport System X-AG ; Potassium Channels ; Calcium

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Contributing Institute(s):

1. U Preclinical Researchers - Bonn (U Preclinical Researchers - Bonn)

Research Program(s):

1. 342 - Disease Mechanisms and Model Systems (POF3-342) (POF3-342)

Appears in the scientific report 2018

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Database coverage:
; ; ; ; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Agriculture, Biology and Environmental Sciences ; Current Contents - Life Sciences ; Current Contents - Physical, Chemical and Earth Sciences ; DOAJ Seal ; IF >= 15 ; JCR ; SCOPUS ; Web of Science Core Collection ; Zoological Record

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Linked articles:

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Journal Article (Erratum/Correction) Savtchenko, L. P. (Corresponding author) ; Bard, L. ; Jensen, T. P. ; Reynolds, J. P. ; Kraev, I. ; Medvedev, N. ; Stewart, M. G. ; Henneberger, C.DZNE* ; Rusakov, D. A.
Author Correction: Disentangling astroglial physiology with a realistic cell model in silico.
Nature Communications 10(1), 5062 (2019) [10.1038/s41467-019-12712-6]2019   Files  Fulltext by Pubmed Central BibTeX | EndNote: XML, Text | RIS

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