%0 Journal Article
%A Savtchenko, Leonid P
%A Bard, Lucie
%A Jensen, Thomas P
%A Reynolds, James P
%A Kraev, Igor
%A Medvedev, Nikolay
%A Stewart, Michael G
%A Henneberger, Christian
%A Rusakov, Dmitri A
%T Disentangling astroglial physiology with a realistic cell model in silico.
%J Nature Communications
%V 9
%N 1
%@ 2041-1723
%C [London]
%I Nature Publishing Group UK
%M DZNE-2020-06499
%P 3554
%D 2018
%X 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.
%K Algorithms
%K Amino Acid Transport System X-AG: metabolism
%K Animals
%K Astrocytes: metabolism
%K Astrocytes: physiology
%K Calcium: metabolism
%K Computer Simulation
%K Hippocampus: cytology
%K Membrane Potentials
%K Models, Neurological
%K Neurons: metabolism
%K Patch-Clamp Techniques
%K Potassium Channels: metabolism
%K Proof of Concept Study
%K Rats
%K Software
%K Amino Acid Transport System X-AG (NLM Chemicals)
%K Potassium Channels (NLM Chemicals)
%K Calcium (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:30177844
%2 pmc:PMC6120909
%R 10.1038/s41467-018-05896-w
%U https://pub.dzne.de/record/140177