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@ARTICLE{Savtchenko:140177,
      author       = {Savtchenko, Leonid P and Bard, Lucie and Jensen, Thomas P
                      and Reynolds, James P and Kraev, Igor and Medvedev, Nikolay
                      and Stewart, Michael G and Henneberger, Christian and
                      Rusakov, Dmitri A},
      title        = {{D}isentangling astroglial physiology with a realistic cell
                      model in silico.},
      journal      = {Nature Communications},
      volume       = {9},
      number       = {1},
      issn         = {2041-1723},
      address      = {[London]},
      publisher    = {Nature Publishing Group UK},
      reportid     = {DZNE-2020-06499},
      pages        = {3554},
      year         = {2018},
      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.},
      keywords     = {Algorithms / Amino Acid Transport System X-AG: metabolism /
                      Animals / Astrocytes: metabolism / Astrocytes: physiology /
                      Calcium: metabolism / Computer Simulation / Hippocampus:
                      cytology / Membrane Potentials / Models, Neurological /
                      Neurons: metabolism / Patch-Clamp Techniques / Potassium
                      Channels: metabolism / Proof of Concept Study / Rats /
                      Software / Amino Acid Transport System X-AG (NLM Chemicals)
                      / Potassium Channels (NLM Chemicals) / Calcium (NLM
                      Chemicals)},
      cin          = {U Preclinical Researchers - Bonn},
      ddc          = {500},
      cid          = {I:(DE-2719)7000005},
      pnm          = {342 - Disease Mechanisms and Model Systems (POF3-342)},
      pid          = {G:(DE-HGF)POF3-342},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:30177844},
      pmc          = {pmc:PMC6120909},
      doi          = {10.1038/s41467-018-05896-w},
      url          = {https://pub.dzne.de/record/140177},
}