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Current applications of mathematical models of the interstitial cells of Cajal in the gastrointestinal tract

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Abstract The interstitial cells of Cajal (ICC) form interconnected networks throughout the gastrointestinal (GI) tract. ICC act as the pacemaker cells that initiate the rhythmic bioelectrical slow waves and intermediary between the GI musculature and nerves, both of which are critical to GI motility. Disruptions to the number of ICC and the integrity of ICC networks have been identified as a key pathophysiological mechanism in a number of clinically challenging GI disorders. The current analyses of ICC generally rely on either functional recordings taken directly from excised tissue or morphological analysis based on images of labeled ICC, where the structural‐functional relationship is investigated in an associative manner rather than mechanistically. On the other hand, computational physiology has played a significant role in facilitating our understanding of a number of physiological systems in both health and disease, and investigations in the GI field are beginning to incorporate several mathematical models of the ICC. The main aim of this review is to present the major modeling advances in GI electrophysiology, in order to introduce a multi‐scale framework for mathematically quantifying the functional consequences of ICC degradation at both cellular and tissue scales. The outcomes will inform future investigators utilizing modeling techniques in their studies. This article is categorized under: Metabolic Diseases > Computational Models
Examples of mathematical ICC models encoded using the CellML standard. (a) Youm et al. model (Youm et al., 2006). (b) Corrias and Buist model (Corrias & Buist, 2008). (c) Lees‐Green et al. model (Lees‐Green, Gibbons, Farrugia, Sneyd, & Cheng, 2014). (d) Faville et al. model (Faville et al., 2009). Other than (b), which simulated gastric slow waves, the remaining models simulated intestinal slow waves, which demonstrate a range of frequencies, resting membrane potentials, and amplitudes
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Simulation of slow wave activity in a mouse gastric ICC‐MP network (862 × 862 × 90 μm) (Avci, Paskaranandavadivel, Du, Vanderwinden, & Cheng, 2020). Shown are (a) potential distribution at one time instant and (b) slow wave velocity profile over the network. We thank Professor JM Vanderwinden for providing the ICC network image
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(a) A three layered tissue model setup with two intramuscular muscle ICC layers (longitudinal muscle [LM] and circumferential muscle [CM] layers), and a myenteric plexus (PM) layer. (b) The LM and CM layers contain preferential conduction in the longitudinal and circumferential direction, respectively. The MP layer conducts slow waves equally in all directions. (c) Time snapshots of the propagation of slow waves in the model under the normal condition and with a conduction block/excision placed at two different orientations. Slow wave propagation is recovered distal to the excision due to the coupled MP layer to the LM and CM layers (Du et al., 2015)
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