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Electrophysiological Modeling of Fibroblasts and their Interaction with Myocytes

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Abstract

Experimental studies have shown that cardiac fibroblasts are electrically inexcitable, but can contribute to electrophysiology of myocardium in various manners. The aim of this computational study was to give insights in the electrophysiological role of fibroblasts and their interaction with myocytes. We developed a mathematical model of fibroblasts based on data from whole-cell patch clamp and polymerase chain reaction (PCR) studies. The fibroblast model was applied together with models of ventricular myocytes to assess effects of heterogeneous intercellular electrical coupling. We investigated the modulation of action potentials of a single myocyte varying the number of coupled fibroblasts and intercellular resistance. Coupling to fibroblasts had only a minor impact on the myocyte’s resting and peak transmembrane voltage, but led to significant changes of action potential duration and upstroke velocity. We examined the impact of fibroblasts on conduction in one-dimensional strands of myocytes. Coupled fibroblasts reduced conduction and upstroke velocity. We studied electrical bridging between ventricular myocytes via fibroblast insets for various coupling resistors. The simulations showed significant conduction delays up to 20.3 ms. In summary, the simulations support strongly the hypothesis that coupling of fibroblasts to myocytes modulates electrophysiology of cardiac cells and tissues.

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Acknowledgments

This work has been supported by the Richard A. and Nora Eccles Fund for Cardiovascular Research, awards from the Nora Eccles Treadwell Foundation (FBS, APM, JAA), and NIH/NHLBI, HL63969 (APM). We thank Ms. Catherine Lloyd, University of Auckland, and Dr. Alan Garny, University of Oxford, for implementing a CellML version of the fibroblast model. We acknowledge the support of Prof. James B. Bassingthwaighte and Dr. Brian Carlson, University of Washington, for implementation of the fibroblast and myocyte-fibroblast models in JSim and including these in the model repository of the NSR Physiome Project (http://www.physiome.org/model/doku.php?id=Cell_Physiology:Fibroblast:model_index and http://www.physiome.org/model/doku.php?id=Cell_Physiology:Action_potential:Myocyte_fibroblast_coupling:model_index).

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  1. Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, 95 S 2000 E, Salt Lake City, UT, 84112, USA

    Frank B. Sachse, Alonso P. Moreno & J. A. Abildskov

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  1. Frank B. Sachse
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Correspondence to Frank B. Sachse.

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Sachse, F.B., Moreno, A.P. & Abildskov, J. . Electrophysiological Modeling of Fibroblasts and their Interaction with Myocytes. Ann Biomed Eng 36, 41–56 (2008). https://doi.org/10.1007/s10439-007-9405-8

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  • DOI: https://doi.org/10.1007/s10439-007-9405-8

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