Gap Junction Dynamics Induces Localized Conductance Bistability in Cardiac Tissue

Hawks, Claudia; Elorza, Jorge; Witt, Annette; Laroze, David; Cantalapiedra, Inma Rodríguez; Peñaranda, Angelina; Echebarria, Blas; Bragard, J.

doi:10.1142/s0218127419300210

Cited by 3 publications

(11 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…15 Here, we have reproduced this dynamical uncoupling at long time scales. Furthermore, we have used a simplified description with a low number of cells to relate the uncoupling to the existence of multistability, thus explaining the previously observed effect 24 of the emergence at a long time scale of a very disordered state with inhomogeneous intercellular conductances. The effect on the action potential conduction velocity of the heterogeneities in the conductance distribution has also been addressed.…”

Section: Discussionmentioning

confidence: 95%

“…Therefore, it is due to a pre-existing heterogeneity of the medium. In a recent publication, 24 we observed that the dispersion in velocity might appear in an utterly homogeneous tissue due to the voltage and time dependence of the intercellular conductance. In the present paper, we will further extend the analysis of the spatially dependent conductances and provide a stability analysis of the mathematical model.…”

Section: Introductionmentioning

confidence: 83%

“…This transition has been studied in a previous publication by the authors. 24 In the latter paper, it was shown that the two states competing are, in fact, two limit cycles with a period equals to the forcing period T = 480 ms. It was also shown that the transition between the two states was sensitive to the initial condition (hysteresis phenomenon) and that the initial noise was also crucial in characterizing this transition.…”

Section: A Multistability Induced By the Shrinking Factor Fsmentioning

confidence: 97%

“…It was shown in a previous study 25 that it is sufficient to couple the gap junction (GJ) dynamics using a monodomain formulation of the cable equation. The same model was used in a recent publication 24 by the authors, where they showed numerical evidence of the multistability phenomenon. For completeness, in this section, we present the model used in Ref.…”

Section: Cable Equation With Gap Junction Dynamicsmentioning

confidence: 99%

“…The purpose of this paper is threefold: first, we review briefly the main result in Ref. 24 and show how the inclusion of the GJ dynamics in the model for the action potential (AP) propagation may lead under some circumstances to spatially nonuniform electrical conductances; second, we explain why this multistability does occur and study it in a reduced system (considering successively only one, two, and three coupled GJs); third, we propose a simplified spatially extended model that captures the characteristics of the full model but with a computational speed gain of over four orders of magnitude. The results of the latter model compare satisfactorily with the full model.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Conductance heterogeneities induced by multistability in the dynamics of coupled cardiac gap junctions

Bragard

Witt²,

Laroze

et al. 2021

Chaos: An Interdisciplinary Journal of Nonlinear Science

Self Cite

View full text Add to dashboard Cite

In this paper, we study the propagation of the cardiac action potential in a one-dimensional fiber, where cells are electrically coupled through gap junctions (GJs). We consider gap junctional gate dynamics that depend on the intercellular potential. We find that different GJs in the tissue can end up in two different states: a low conducting state and a high conducting state. We first present evidence of the dynamical multistability that occurs by setting specific parameters of the GJ dynamics. Subsequently, we explain how the multistability is a direct consequence of the GJ stability problem by reducing the dynamical system's dimensions. The conductance dispersion usually occurs on a large time scale, i.e., thousands of heartbeats. The full cardiac model simulations are computationally demanding, and we derive a simplified model that allows for a reduction in the computational cost of four orders of magnitude. This simplified model reproduces nearly quantitatively the results provided by the original full model. We explain the discrepancies between the two models due to the simplified model's lack of spatial correlations. This simplified model provides a valuable tool to explore cardiac dynamics over very long time scales. That is highly relevant in studying diseases that develop on a large time scale compared to the basic heartbeat. As in the brain, plasticity and tissue remodeling are crucial parameters in determining the action potential wave propagation's stability.

show abstract

Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 83%

Section: A Multistability Induced By the Shrinking Factor Fsmentioning

confidence: 97%

Section: Cable Equation With Gap Junction Dynamicsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Conductance heterogeneities induced by multistability in the dynamics of coupled cardiac gap junctions

Bragard

Witt²,

Laroze

et al. 2021

Chaos: An Interdisciplinary Journal of Nonlinear Science

Self Cite

View full text Add to dashboard Cite

show abstract

A simple approach for image-based modelling of the heart that enables robust simulation of highly heterogeneous electrical excitation

Colman,

Benson

2023

Sci Rep

View full text Add to dashboard Cite

Remodelling of cardiac tissue structure, including intercellular electrical coupling, is a major determinant of the complex and heterogeneous excitation patterns associated with cardiac arrhythmias. Evaluation of the precise mechanisms by which local tissue structure determines global arrhythmic excitation patterns is a major challenge that may be critically important for the development of effective treatment strategies. Computational modelling is a key tool in the study of cardiac arrhythmias, yet the established approaches for organ-scale modelling are unsuitable to capture the impact of local conduction heterogeneities; a novel approach is required to provide this multi-scale mechanistic insight. We present a fundamentally simple yet powerful approach to simulate electrical excitation in highly heterogeneous whole-heart models that exploits the underlying discreteness of the myocardium. Preliminary simulations demonstrate that this approach can capture lower conduction velocities and reproduce wave breakdown and the development of re-entry in a range of conditions.

show abstract

A simple approach for image-based modelling of the heart that enables robust simulation of highly heterogeneous electrical excitation

Colman

Benson

2022

Preprint

View full text Add to dashboard Cite

Inter-cellular electrical coupling in the heart is a major determinant of excitation patterns in health and disease. Cardiac arrhythmias, in particular rapid arrhythmias such as tachycardia and fibrillation, are characterised by spatially complex and heterogeneous conduction patterns. In disease conditions, these complex excitation patterns may result from electrophysiological and structural remodelling, for example, remodelling of inter-cellular gap junctions and/or the proliferation of fibrosis. Evaluation of the precise mechanisms by which local tissue structure determines global arrhythmic excitation patterns is a major challenge, yet may be critically important for the development of effective treatment strategies. Computational modelling is a viable tool to address this challenge, but the established approaches for organ-scale simulations are unsuitable to capture the impact of local conduction heterogeneities. In this study, we present a novel network model of inter-cellular coupling for anisotropic organ-scale simulation of electrical dynamics that enables cellular connections to be heterogeneously interrupted. The presented approach is both simple and powerful. Intercellular coupling strength is weighted based on local myocyte orientation and can be easily modified by sampling from continuous distributions and/or removing individual cellular connections entirely; both approaches can be differentially applied to axial and transverse cellular connections for full control over the conduction substrate. Preliminary simulations demonstrate the value of such an approach and indicate that perturbing cellular connections in this manner can facilitate lower global conduction velocities and capture wave breakdown and the development of re-entry in a way that is not possible with the previously established approaches. Therefore, we have presented a useful model to simulate the impact of local conduction heterogeneity in organ-scale models that expands the scope and possibilities for computational models to elucidate arrhythmia mechanisms and generate genuine subject-specificity, which may be particularly relevant in disease conditions.

show abstract

Gap Junction Dynamics Induces Localized Conductance Bistability in Cardiac Tissue

Cited by 3 publications

References 44 publications

Conductance heterogeneities induced by multistability in the dynamics of coupled cardiac gap junctions

Conductance heterogeneities induced by multistability in the dynamics of coupled cardiac gap junctions

A simple approach for image-based modelling of the heart that enables robust simulation of highly heterogeneous electrical excitation

A simple approach for image-based modelling of the heart that enables robust simulation of highly heterogeneous electrical excitation

Contact Info

Product

Resources

About