title: Mathematical investigation of IP3-dependent calcium dynamics in astrocytes.
abstract: We study evoked calcium dynamics in astrocytes, a major cell type in the mammalian brain. Experimental evidence has shown that such dynamics are highly variable between different trials, cells, and cell subcompartments. Here we present a qualitative analysis of a recent mathematical model of astrocyte calcium responses. We show how the major response types are generated in the model as a result of the underlying bifurcation structure. By varying key channel parameters, mimicking blockers used by experimentalists, we manipulate this underlying bifurcation structure and predict how the distributions of responses can change. We find that store-operated calcium channels, plasma membrane bound channels with little activity during calcium transients, have a surprisingly strong effect, underscoring the importance of considering these channels in both experiments and mathematical settings. Variation in the maximum flow in different calcium channels is also shown to determine the range of stable oscillations, as well as set the range of frequencies of the oscillations. Further, by conducting a randomized search through the parameter space and recording the resulting calcium responses, we create a database that can be used by experimentalists to help estimate the underlying channel distribution of their cells.
authors.affiliation: Department of Mathematics, University of Utah, Salt Lake City, UT, 84112, USA.
authors.forename: Gregory
authors.initials: G
authors.lastname: Handy
authors.affiliation: Department of Bioengineering, University of Utah, Salt Lake City, UT, 84112, USA.
authors.forename: Marsa
authors.initials: M
authors.lastname: Taheri
authors.affiliation: Department of Biomedical Engineering, Boston University, Boston, MA, 02215, USA.
authors.forename: John A
authors.initials: JA
authors.lastname: White
authors.affiliation: Department of Mathematics, University of Utah, Salt Lake City, UT, 84112, USA. borisyuk@math.utah.edu.
authors.forename: Alla
authors.identifier: http://orcid.org/0000-0001-8412-215X
authors.initials: A
authors.lastname: Borisyuk
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels; D020013:Calcium Signaling; D008959:Models, Neurological
chemical_list: D015220:Calcium Channels; D002118:Calcium
keywords: Astrocytes; Calcium response; Hopf Bifurcation; Store operated calcium channels