Fibroblast mediated dynamics in diffusively uncoupled myocytes: a simulation study using 2-cell motifs
Abstract In healthy hearts myocytes are typically coupled to nearest neighbours through gap junctions. Under pathological conditions such as fibrosis, or in scar tissue, or across ablation lines myocytes can uncouple from their neighbours. Electrical conduction may still occur via fibroblasts that n...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-02-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-024-54564-1 |
| _version_ | 1797274636715556864 |
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| author | S. Sridhar Richard H. Clayton |
| author_facet | S. Sridhar Richard H. Clayton |
| author_sort | S. Sridhar |
| collection | DOAJ |
| description | Abstract In healthy hearts myocytes are typically coupled to nearest neighbours through gap junctions. Under pathological conditions such as fibrosis, or in scar tissue, or across ablation lines myocytes can uncouple from their neighbours. Electrical conduction may still occur via fibroblasts that not only couple proximal myocytes but can also couple otherwise unconnected regions. We hypothesise that such coupling can alter conduction between myocytes via introduction of delays or by initiation of premature stimuli that can potentially result in reentry or conduction blocks. To test this hypothesis we have developed several 2-cell motifs and investigated the effect of fibroblast mediated electrical coupling between uncoupled myocytes. We have identified various regimes of myocyte behaviour that depend on the strength of gap-junctional conductance, connection topology, and parameters of the myocyte and fibroblast models. These motifs are useful in developing a mechanistic understanding of long-distance coupling on myocyte dynamics and enable the characterisation of interaction between different features such as myocyte and fibroblast properties, coupling strengths and pacing period. They are computationally inexpensive and allow for incorporation of spatial effects such as conduction velocity. They provide a framework for constructing scar tissue boundaries and enable linking of cellular level interactions with scar induced arrhythmia. |
| first_indexed | 2024-03-07T15:01:09Z |
| format | Article |
| id | doaj.art-2def6ce8e0be4d03bccf30daae61bdb9 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-07T15:01:09Z |
| publishDate | 2024-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-2def6ce8e0be4d03bccf30daae61bdb92024-03-05T19:07:48ZengNature PortfolioScientific Reports2045-23222024-02-0114111310.1038/s41598-024-54564-1Fibroblast mediated dynamics in diffusively uncoupled myocytes: a simulation study using 2-cell motifsS. Sridhar0Richard H. Clayton1Department of Computer Science, University of SheffieldDepartment of Computer Science, University of SheffieldAbstract In healthy hearts myocytes are typically coupled to nearest neighbours through gap junctions. Under pathological conditions such as fibrosis, or in scar tissue, or across ablation lines myocytes can uncouple from their neighbours. Electrical conduction may still occur via fibroblasts that not only couple proximal myocytes but can also couple otherwise unconnected regions. We hypothesise that such coupling can alter conduction between myocytes via introduction of delays or by initiation of premature stimuli that can potentially result in reentry or conduction blocks. To test this hypothesis we have developed several 2-cell motifs and investigated the effect of fibroblast mediated electrical coupling between uncoupled myocytes. We have identified various regimes of myocyte behaviour that depend on the strength of gap-junctional conductance, connection topology, and parameters of the myocyte and fibroblast models. These motifs are useful in developing a mechanistic understanding of long-distance coupling on myocyte dynamics and enable the characterisation of interaction between different features such as myocyte and fibroblast properties, coupling strengths and pacing period. They are computationally inexpensive and allow for incorporation of spatial effects such as conduction velocity. They provide a framework for constructing scar tissue boundaries and enable linking of cellular level interactions with scar induced arrhythmia.https://doi.org/10.1038/s41598-024-54564-1 |
| spellingShingle | S. Sridhar Richard H. Clayton Fibroblast mediated dynamics in diffusively uncoupled myocytes: a simulation study using 2-cell motifs Scientific Reports |
| title | Fibroblast mediated dynamics in diffusively uncoupled myocytes: a simulation study using 2-cell motifs |
| title_full | Fibroblast mediated dynamics in diffusively uncoupled myocytes: a simulation study using 2-cell motifs |
| title_fullStr | Fibroblast mediated dynamics in diffusively uncoupled myocytes: a simulation study using 2-cell motifs |
| title_full_unstemmed | Fibroblast mediated dynamics in diffusively uncoupled myocytes: a simulation study using 2-cell motifs |
| title_short | Fibroblast mediated dynamics in diffusively uncoupled myocytes: a simulation study using 2-cell motifs |
| title_sort | fibroblast mediated dynamics in diffusively uncoupled myocytes a simulation study using 2 cell motifs |
| url | https://doi.org/10.1038/s41598-024-54564-1 |
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