Models of cardiomyocyte-non-myocyte electrical interactions
Ana Simon-Chica1, Axel Loewe2, Peter Kohl3
1Novel Arrhythmogenic Mechanisms Program, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain.
The Journal of Physiology
|July 1, 2025
Summary
Cardiac non-muscle cells, like fibroblasts and macrophages, actively influence heart electrical activity through electrotonic coupling with cardiomyocytes. Computational models are crucial for understanding these complex cell interactions in cardiac electrophysiology.
Area of Science:
- Cardiovascular Physiology
- Computational Biology
- Cardiac Electrophysiology
Background:
- Cardiac non-myocytes, including fibroblasts and macrophages, are increasingly recognized for their roles in cardiac electrophysiology.
- Evidence shows these cells form electrotonic connections with cardiomyocytes (CM), challenging traditional views of cardiac electrical signaling.
- In situ study of heterocellular coupling is experimentally challenging, highlighting the need for computational approaches.
Purpose of the Study:
- To provide an overview of computational models simulating heterocellular coupling in the heart.
- To discuss the rationale for studying cardiac heterocellular coupling based on clinical and experimental findings.
- To explore the application of computational modeling across various spatial scales, from single cells to whole organs.
Main Methods:
- Review of existing literature on computational modeling of cardiac heterocellular coupling.
- Analysis of models simulating electrotonic interactions between cardiomyocytes and non-myocytes (fibroblasts, macrophages).
- Examination of models across different spatial scales (single-cell, tissue, whole-organ).
Main Results:
- Computational models offer a viable approach to investigate complex heterocellular coupling dynamics that are difficult to study experimentally.
- Models can simulate electrotonic interactions at single-cell and larger scales, providing insights into their functional impact.
- The review synthesizes current modeling strategies for understanding the contribution of non-myocytes to cardiac electrophysiology.
Conclusions:
- Computational modeling is essential for advancing our understanding of cardiac electrophysiology in light of the active roles of non-myocytes.
- Future research should leverage and expand upon these computational tools to further elucidate heterocellular coupling mechanisms.
- A conceptual shift in cardiac electrophysiology is needed to incorporate the influence of non-myocyte-cardiomyocyte interactions.
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