Models of cardiomyocyte–non‐myocyte electrical interactions

Figures

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  Figure 1. Conceptual illustration of cardiomyocyte–non‐myocyte (CM–NM) electrotonic interactions. Left, histological images showing connexin43 (green dots), CM (striated red) and fibroblasts (red, F) in A and B, and Lucifer yellow spread through a heterocellular chain of CM and fibroblasts in C. Right, computational modelling of electrical crosstalk of CM (red) and NM (green) in three scenarios. A, in ‘zero‐sided coupling’ where NM and CM are electrically insulated from one‐another, the CM action potential (AP) (red curve) is not affected by the fibroblast (green curve, showing a resting membrane potential of about ‐30 mV). B, in ‘single‐sided coupling’ where NM are connected to CM that are themselves well‐coupled, CM can ‘AP‐clamp’ a fibroblast. C, in ‘double‐sided coupling’, NM interlink groups of CM that are not otherwise in direct contact. This can support passive conduction of AP‐like signals from one group of CM (top) and trigger de novo generation of an AP in more distal CM. While zero‐sided coupling presumably dominates in physiological settings, single‐sided coupling may arise in reactive interstitial fibrosis (e.g. in chronic haemodynamic overload), and double‐sided connection…

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  Figure 2. Timeline of select milestones in cardiomyocyte–non‐myocyte (CM–NM) interaction modelling. The left panels highlight two NM modelling approaches: passive (where NM are represented as a passive Ohmic resistance and capacitance) and active (illustrating that NM contain different ion channels). The middle panel provides examples of modelling studies addressing CM–NM heterocellular crosstalk. The corresponding literature references are, from bottom to top: Hulsmans et al., 2017; Ivanocic & Kucera, 2021; Jacquemet & Henriquez, 2008, 2007; Kohl et al., 1994b; Kucera et al., 2002; MacCannell et al., 2007; Maleckar et al., 2009; McDowell et al., 2011; Morgan et al., 2016; Simon‐Chica et al., 2022; Sachse et al., 2008; Xie, Garfinkel, Camelliti et al., 2009. The references included are a subset of pioneering contributions that have helped to define models which are in widespread use within the scientific community. The right panel illustrates different spatial scales addressed, from pairs of 0D (Kohl & Noble, 1996) single‐cell models and their interactions in early studies, to integrative frameworks capturing 1D (Simon‐Chica et al., 2023), 2D (modified from openCARP), and whole‐heart 3D…