Multiscale Modeling Indicates That Temperature Dependent [Ca2+]i Spiking in Astrocytes Is Quantitatively Consistent with Modulated SERCA Activity.
Changes in the cytosolic Ca(2+) concentration ([Ca(2+)]i) are the most predominant active signaling mechanism in astrocytes that can modulate neuronal activity and is assumed to influence neuronal plasticity. Although Ca(2+) signaling in astrocytes has been intensively studied in the past, our understanding of the signaling mechanism and its impact on tissue level is still incomplete. Here we revisit our previously published data on the strong temperature dependence of Ca(2+) signals in both cultured primary astrocytes and astrocytes in acute brain slices of mice. We apply multiscale modeling to test the hypothesis that the temperature dependent [Ca(2+)]i spiking is mainly caused by the increased activity of the sarcoendoplasmic reticulum ATPases (SERCAs) that remove Ca(2+) from the cytosol into the endoplasmic reticulum. Quantitative comparison of experimental data with multiscale simulations supports the SERCA activity hypothesis. Further analysis of multiscale modeling and traditional rate equations indicates that the experimental observations are a spatial phenomenon where increasing pump strength leads to a decoupling of Ca(2+) release sites and subsequently to vanishing [Ca(2+)]i spikes.
Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 7 Avenue des Hauts-Fourneaux, 4362 Esch-sur-Alzette, Luxembourg ; National Centre for Microscopy and Imaging Research, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0608, USA.
Niko
N
Komin
Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 7 Avenue des Hauts-Fourneaux, 4362 Esch-sur-Alzette, Luxembourg.
Mahsa
M
Moein
National Centre for Microscopy and Imaging Research, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0608, USA.
Mark H
MH
Ellisman
Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 7 Avenue des Hauts-Fourneaux, 4362 Esch-sur-Alzette, Luxembourg ; National Centre for Microscopy and Imaging Research, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0608, USA.
Alexander
A
Skupin
D000465:Algorithms; D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D020013:Calcium Signaling / Q000502:physiology*; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000502:physiology; D007700:Kinetics; D051379:Mice; D008959:Models, Neurological; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000502:physiology*; D013696:Temperature
D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases