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Verma2016 - Ca(2+) Signal Propagation Along Hepatocyte Cords


ABSTRACT: Verma2016 - Ca(2+) Signal Propagation Along Hepatocyte Cords This model is described in the article: Computational Modeling of Spatiotemporal Ca(2+) Signal Propagation Along Hepatocyte Cords. Verma A, Makadia H, Hoek JB, Ogunnaike BA, Vadigepalli R. IEEE Trans Biomed Eng 2016 Oct; 63(10): 2047-2055 Abstract: The purpose of this study is to model the dynamics of lobular Ca(2+) wave propagation induced by an extracellular stimulus, and to analyze the effect of spatially systematic variations in cell-intrinsic signaling parameters on sinusoidal Ca(2+) response.We developed a computational model of lobular scale Ca(2+) signaling that accounts for receptor- mediated initiation of cell-intrinsic Ca(2+) signal in hepatocytes and its propagation to neighboring hepatocytes through gap junction-mediated molecular exchange.Analysis of the simulations showed that a pericentral-to-periportal spatial gradient in hormone sensitivity and/or rates of IP3 synthesis underlies the Ca(2+) wave propagation. We simulated specific cases corresponding to localized disruptions in the graded pattern of these parameters along a hepatic sinusoid. Simulations incorporating locally altered parameters exhibited Ca(2+) waves that do not propagate throughout the hepatic plate. Increased gap junction coupling restored normal Ca(2+) wave propagation when hepatocytes with low Ca(2+) signaling ability were localized in the midlobular or the pericentral region.Multiple spatial patterns in intracellular signaling parameters can lead to Ca(2+) wave propagation that is consistent with the experimentally observed spatial patterns of Ca(2+) dynamics. Based on simulations and analysis, we predict that increased gap junction-mediated intercellular coupling can induce robust Ca(2+) signals in otherwise poorly responsive hepatocytes, at least partly restoring the sinusoidally oriented Ca (2+) waves.Our bottom-up model of agonist-evoked spatial Ca(2+) patterns can be integrated with detailed descriptions of liver histology to study Ca(2+) regulation at the tissue level. This model is hosted on BioModels Database and identified by: MODEL1603110003. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

SUBMITTER: Aalap Verma  

PROVIDER: BIOMD0000000834 | BioModels | 2024-09-02

REPOSITORIES: BioModels

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Computational Modeling of Spatiotemporal Ca(2+) Signal Propagation Along Hepatocyte Cords.

Verma Aalap A   Makadia Hirenkumar H   Hoek Jan B JB   Ogunnaike Babatunde A BA   Vadigepalli Rajanikanth R  

IEEE transactions on bio-medical engineering 20160404 10


<h4>Objective</h4>The purpose of this study is to model the dynamics of lobular Ca(2+) wave propagation induced by an extracellular stimulus, and to analyze the effect of spatially systematic variations in cell-intrinsic signaling parameters on sinusoidal Ca(2+) response.<h4>Methods</h4>We developed a computational model of lobular scale Ca(2+) signaling that accounts for receptor- mediated initiation of cell-intrinsic Ca(2+) signal in hepatocytes and its propagation to neighboring hepatocytes t  ...[more]

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