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Statistical Modeling in Biomedical Research pp 355–377Cite as

Mathematical Model of Mouse Ventricular Myocytes Overexpressing Adenylyl Cyclase Type 5

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Part of the book series: Emerging Topics in Statistics and Biostatistics ((ETSB))

Abstract

A compartmentalized mathematical model of transgenic (TG) mouse ventricular myocytes overexpressing adenylyl cyclase type 5 was developed. The model describes well β1- and β2-adrenergic signaling systems consisting of β1- and β2-adrenergic receptors (β1-ARs and β2-ARs), stimulatory and inhibitory G proteins (Gs and Gi), adenylyl cyclases types 4–7 (AC4–7), phosphodiesterases type 2–4 (PDE2–4), protein kinase A (PKA), protein phosphatases type 1 and 2A (PP1 and PP2A), G-protein receptor kinase type 2 (GRK2), heat-stable protein kinase inhibitor (PKI), and the inhibitor-1 (I-1). We found that the overexpression of AC5 resulted in an increased basal cAMP production, leading to an increased activation of PKA, prolongation of the action potential, and increased [Ca2+]i transient. Simulation results suggest blunted response of TG ventricular cells to the stimulation of β-adrenergic signaling system with isoproterenol comparing to wild type (WT) cells. Simulations of spontaneous Ca2+ release showed larger magnitudes of DADs in TG as compared to WT mice. Modeling data were compared to the experimental data obtained from TG mice overexpressing AC5 as well as to the simulations obtained with the mathematical model for WT mice.

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Author information

Authors and Affiliations

  1. Department of Mathematics and Statistics, Georgia State University, Atlanta, GA, USA

    Vladimir E. Bondarenko

  2. Neuroscience Institute, Georgia State University, Atlanta, GA, USA

    Vladimir E. Bondarenko

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  1. Vladimir E. Bondarenko
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Correspondence to Vladimir E. Bondarenko .

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Editors and Affiliations

  1. Math and Statistics, 1342, Georgia State University, Atlanta, GA, USA

    Yichuan Zhao

  2. School of Social Work, University of North Carolina, Chapel Hill, NC, USA

    Ding-Geng (Din) Chen

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Bondarenko, V.E. (2020). Mathematical Model of Mouse Ventricular Myocytes Overexpressing Adenylyl Cyclase Type 5. In: Zhao, Y., Chen, DG. (eds) Statistical Modeling in Biomedical Research. Emerging Topics in Statistics and Biostatistics . Springer, Cham. https://doi.org/10.1007/978-3-030-33416-1_16

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