Fibroblast mediated dynamics in diffusively uncoupled myocytes -- a simulation study using 2-cell motifs

TL;DR

This study uses 2-cell simulation motifs to explore how fibroblast-mediated coupling affects electrical conduction in uncoupled cardiac myocytes, revealing regimes that influence arrhythmia development.

Contribution

It introduces a computational framework using simple 2-cell motifs to understand fibroblast-mediated long-distance coupling effects on myocyte dynamics.

Findings

Identified regimes of myocyte behavior based on coupling strength and topology.

Demonstrated how fibroblast coupling can induce delays or premature stimuli.

Provided a computationally inexpensive model for studying scar tissue effects.

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.