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000140177 1001_ $$0P:(DE-HGF)0$$aSavtchenko, Leonid P$$b0$$eCorresponding author
000140177 245__ $$aDisentangling astroglial physiology with a realistic cell model in silico.
000140177 260__ $$a[London]$$bNature Publishing Group UK$$c2018
000140177 264_1 $$2Crossref$$3online$$bSpringer Science and Business Media LLC$$c2018-09-03
000140177 264_1 $$2Crossref$$3print$$bSpringer Science and Business Media LLC$$c2018-12-01
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000140177 520__ $$aElectrically non-excitable astroglia take up neurotransmitters, buffer extracellular K+ and generate Ca2+ signals that release molecular regulators of neural circuitry. The underlying machinery remains enigmatic, mainly because the sponge-like astrocyte morphology has been difficult to access experimentally or explore theoretically. Here, we systematically incorporate multi-scale, tri-dimensional astroglial architecture into a realistic multi-compartmental cell model, which we constrain by empirical tests and integrate into the NEURON computational biophysical environment. This approach is implemented as a flexible astrocyte-model builder ASTRO. As a proof-of-concept, we explore an in silico astrocyte to evaluate basic cell physiology features inaccessible experimentally. Our simulations suggest that currents generated by glutamate transporters or K+ channels have negligible distant effects on membrane voltage and that individual astrocytes can successfully handle extracellular K+ hotspots. We show how intracellular Ca2+ buffers affect Ca2+ waves and why the classical Ca2+ sparks-and-puffs mechanism is theoretically compatible with common readouts of astroglial Ca2+ imaging.
000140177 536__ $$0G:(DE-HGF)POF3-342$$a342 - Disease Mechanisms and Model Systems (POF3-342)$$cPOF3-342$$fPOF III$$x0
000140177 542__ $$2Crossref$$i2018-09-03$$uhttps://creativecommons.org/licenses/by/4.0
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000140177 650_7 $$2NLM Chemicals$$aAmino Acid Transport System X-AG
000140177 650_7 $$2NLM Chemicals$$aPotassium Channels
000140177 650_7 $$0SY7Q814VUP$$2NLM Chemicals$$aCalcium
000140177 650_2 $$2MeSH$$aAlgorithms
000140177 650_2 $$2MeSH$$aAmino Acid Transport System X-AG: metabolism
000140177 650_2 $$2MeSH$$aAnimals
000140177 650_2 $$2MeSH$$aAstrocytes: metabolism
000140177 650_2 $$2MeSH$$aAstrocytes: physiology
000140177 650_2 $$2MeSH$$aCalcium: metabolism
000140177 650_2 $$2MeSH$$aComputer Simulation
000140177 650_2 $$2MeSH$$aHippocampus: cytology
000140177 650_2 $$2MeSH$$aMembrane Potentials
000140177 650_2 $$2MeSH$$aModels, Neurological
000140177 650_2 $$2MeSH$$aNeurons: metabolism
000140177 650_2 $$2MeSH$$aPatch-Clamp Techniques
000140177 650_2 $$2MeSH$$aPotassium Channels: metabolism
000140177 650_2 $$2MeSH$$aProof of Concept Study
000140177 650_2 $$2MeSH$$aRats
000140177 650_2 $$2MeSH$$aSoftware
000140177 7001_ $$0P:(DE-HGF)0$$aBard, Lucie$$b1
000140177 7001_ $$0P:(DE-HGF)0$$aJensen, Thomas P$$b2
000140177 7001_ $$0P:(DE-HGF)0$$aReynolds, James P$$b3
000140177 7001_ $$0P:(DE-HGF)0$$aKraev, Igor$$b4
000140177 7001_ $$0P:(DE-HGF)0$$aMedvedev, Nikolay$$b5
000140177 7001_ $$0P:(DE-HGF)0$$aStewart, Michael G$$b6
000140177 7001_ $$0P:(DE-2719)2811625$$aHenneberger, Christian$$b7$$udzne
000140177 7001_ $$0P:(DE-HGF)0$$aRusakov, Dmitri A$$b8
000140177 77318 $$2Crossref$$3journal-article$$a10.1038/s41467-018-05896-w$$b : Springer Science and Business Media LLC, 2018-09-03$$n1$$p3554$$tNature Communications$$v9$$x2041-1723$$y2018
000140177 773__ $$0PERI:(DE-600)2553671-0$$a10.1038/s41467-018-05896-w$$gVol. 9, no. 1, p. 3554$$n1$$p3554$$q9:1<3554$$tNature Communications$$v9$$x2041-1723$$y2018
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000140177 8567_ $$2Pubmed Central$$uhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC6120909
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