TY  - JOUR
AU  - Savtchenko, Leonid P
AU  - Bard, Lucie
AU  - Jensen, Thomas P
AU  - Reynolds, James P
AU  - Kraev, Igor
AU  - Medvedev, Nikolay
AU  - Stewart, Michael G
AU  - Henneberger, Christian
AU  - Rusakov, Dmitri A
TI  - Disentangling astroglial physiology with a realistic cell model in silico.
JO  - Nature Communications
VL  - 9
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Nature Publishing Group UK
M1  - DZNE-2020-06499
SP  - 3554
PY  - 2018
AB  - 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.
KW  - Algorithms
KW  - Amino Acid Transport System X-AG: metabolism
KW  - Animals
KW  - Astrocytes: metabolism
KW  - Astrocytes: physiology
KW  - Calcium: metabolism
KW  - Computer Simulation
KW  - Hippocampus: cytology
KW  - Membrane Potentials
KW  - Models, Neurological
KW  - Neurons: metabolism
KW  - Patch-Clamp Techniques
KW  - Potassium Channels: metabolism
KW  - Proof of Concept Study
KW  - Rats
KW  - Software
KW  - Amino Acid Transport System X-AG (NLM Chemicals)
KW  - Potassium Channels (NLM Chemicals)
KW  - Calcium (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:30177844
C2  - pmc:PMC6120909
DO  - DOI:10.1038/s41467-018-05896-w
UR  - https://pub.dzne.de/record/140177
ER  -