Multiscale Modeling Indicates That Temperature Dependent [Ca2+]i Spiking in Astrocytes Is Quantitatively Consistent with Modulated SERCA Activity

Changes in the cytosolic Ca2+ concentration ([Ca2+]i) are the most predominant active signaling mechanism in astrocytes that can modulate neuronal activity and is assumed to influence neuronal plasticity. Although Ca2+ signaling in astrocytes has been intensively studied in the past, our understandi...

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Main Authors: Niko Komin, Mahsa Moein, Mark H. Ellisman, Alexander Skupin
Format: Article
Language:English
Published: Wiley 2015-01-01
Series:Neural Plasticity
Online Access:http://dx.doi.org/10.1155/2015/683490
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author Niko Komin
Mahsa Moein
Mark H. Ellisman
Alexander Skupin
author_facet Niko Komin
Mahsa Moein
Mark H. Ellisman
Alexander Skupin
author_sort Niko Komin
collection DOAJ
description Changes in the cytosolic Ca2+ concentration ([Ca2+]i) are the most predominant active signaling mechanism in astrocytes that can modulate neuronal activity and is assumed to influence neuronal plasticity. Although Ca2+ 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 Ca2+ 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 [Ca2+]i spiking is mainly caused by the increased activity of the sarcoendoplasmic reticulum ATPases (SERCAs) that remove Ca2+ 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 Ca2+ release sites and subsequently to vanishing [Ca2+]i spikes.
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institution Kabale University
issn 2090-5904
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publishDate 2015-01-01
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spelling doaj-art-79432d1f1ed74a20bf5c0923a50e05b42025-02-03T06:14:04ZengWileyNeural Plasticity2090-59041687-54432015-01-01201510.1155/2015/683490683490Multiscale Modeling Indicates That Temperature Dependent [Ca2+]i Spiking in Astrocytes Is Quantitatively Consistent with Modulated SERCA ActivityNiko Komin0Mahsa Moein1Mark H. Ellisman2Alexander Skupin3Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 7 Avenue des Hauts-Fourneaux, 4362 Esch-sur-Alzette, LuxembourgLuxembourg Centre for Systems Biomedicine, University of Luxembourg, 7 Avenue des Hauts-Fourneaux, 4362 Esch-sur-Alzette, LuxembourgNational Centre for Microscopy and Imaging Research, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0608, USALuxembourg Centre for Systems Biomedicine, University of Luxembourg, 7 Avenue des Hauts-Fourneaux, 4362 Esch-sur-Alzette, LuxembourgChanges in the cytosolic Ca2+ concentration ([Ca2+]i) are the most predominant active signaling mechanism in astrocytes that can modulate neuronal activity and is assumed to influence neuronal plasticity. Although Ca2+ 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 Ca2+ 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 [Ca2+]i spiking is mainly caused by the increased activity of the sarcoendoplasmic reticulum ATPases (SERCAs) that remove Ca2+ 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 Ca2+ release sites and subsequently to vanishing [Ca2+]i spikes.http://dx.doi.org/10.1155/2015/683490
spellingShingle Niko Komin
Mahsa Moein
Mark H. Ellisman
Alexander Skupin
Multiscale Modeling Indicates That Temperature Dependent [Ca2+]i Spiking in Astrocytes Is Quantitatively Consistent with Modulated SERCA Activity
Neural Plasticity
title Multiscale Modeling Indicates That Temperature Dependent [Ca2+]i Spiking in Astrocytes Is Quantitatively Consistent with Modulated SERCA Activity
title_full Multiscale Modeling Indicates That Temperature Dependent [Ca2+]i Spiking in Astrocytes Is Quantitatively Consistent with Modulated SERCA Activity
title_fullStr Multiscale Modeling Indicates That Temperature Dependent [Ca2+]i Spiking in Astrocytes Is Quantitatively Consistent with Modulated SERCA Activity
title_full_unstemmed Multiscale Modeling Indicates That Temperature Dependent [Ca2+]i Spiking in Astrocytes Is Quantitatively Consistent with Modulated SERCA Activity
title_short Multiscale Modeling Indicates That Temperature Dependent [Ca2+]i Spiking in Astrocytes Is Quantitatively Consistent with Modulated SERCA Activity
title_sort multiscale modeling indicates that temperature dependent ca2 i spiking in astrocytes is quantitatively consistent with modulated serca activity
url http://dx.doi.org/10.1155/2015/683490
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AT mahsamoein multiscalemodelingindicatesthattemperaturedependentca2ispikinginastrocytesisquantitativelyconsistentwithmodulatedsercaactivity
AT markhellisman multiscalemodelingindicatesthattemperaturedependentca2ispikinginastrocytesisquantitativelyconsistentwithmodulatedsercaactivity
AT alexanderskupin multiscalemodelingindicatesthattemperaturedependentca2ispikinginastrocytesisquantitativelyconsistentwithmodulatedsercaactivity