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.

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SUBMITTER: Lucian Smith 

PROVIDER: MODEL1603110003 | biostudies-other |

SECONDARY ACCESSION(S): 27076052

REPOSITORIES: biostudies-other