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Updated: Mar 8, 2026
Patient-specific Modeling of the Heart: Estimation of Ventricular Fiber Orientations
Published on: January 8, 2013
Why not to include M-cells in ventricular computer models
Bas Boukens1, Mark Potse2, Edward J Vigmond3
1Department of Cardiology, Laboratory of Experimental Cardiology, Leiden University Medical Center, Leiden, the Netherlands; Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands.
Insights
M-cells, proposed to have extremely long action potential durations (APD), are not consistently found across species and do not explain electrocardiograms. Therefore, these specialized cardiomyocytes should not be included in ventricular computer models.
Area of Science:
- Cardiology
- Computational Biology
- Electrophysiology
Background:
- Cardiomyocytes exhibit heterogeneous action potential durations (APD) across the ventricles.
- The existence of M-cells with extremely long APDs in the midmyocardium, primarily based on canine models, has been proposed.
- M-cells are currently incorporated into computational models of the ventricles.
Purpose of the Study:
- To review experimental evidence regarding the presence and characteristics of M-cells in different species.
- To evaluate the necessity and impact of including M-cells in computational models of ventricular electrophysiology.
- To argue against the inclusion of M-cells in ventricular computer models.
Main Methods:
- Review of experimental findings from multiple research groups investigating M-cells in various species.
- Analysis of computer simulations to assess the role of M-cells in electrocardiogram generation and physiological behavior.
- Evaluation of M-cell APD characteristics at different pacing rates, including rates below sinus rhythm.
Main Results:
- M-cells are not consistently found in the same locations or as a significant band across species, unlike in the canine wedge model.
- Computer simulations indicate that M-cells are not essential for explaining the electrocardiogram and may lead to non-physiological outcomes.
- M-cell-specific prolonged action potential duration is only observed at pacing rates significantly slower than physiological sinus rhythm and would not manifest during arrhythmias.
Conclusions:
- There is insufficient evidence for a M-cell population large enough to influence transmural APD.
- The inclusion of M-cells in ventricular computer models is not necessary and may introduce inaccuracies.
- M-cells should be excluded from future computational models of the ventricles.
Abstract:
Cardiomyocytes show considerable heterogeneity in action potential duration (APD) throughout the ventricles. Based on canine experiments, it has been proposed that a population of cells exhibiting extremely long APDs, the M-cells, is present in the midmyocardium. This cell type continues to be used in simulation studies. In this review, however, we argue against including them in computer models of the ventricles. Our argument is based on experimental findings reported by other research groups who have looked for M-cells in several species. Other than in the canine wedge model, M-cells are neither found consistently in the same locations nor as a large band, but rather as sparse, small islands. Using computer simulations, we demonstrate that M-cells are not required to explain the electrocardiogram and that their inclusion may result in non-physiological behaviour. Finally, as initially proposed, M-cells only manifest prolonged APD at extremely slow pacing rates, below sinus rhythm, and would not be seen in arrhythmias. Therefore, we conclude that there is no proof of a large enough population of M-cells to affect transmural APD, nor is it necessary, so M-cells should not be included in computer models.
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