Multiscale Modeling of Gastrointestinal Electrophysiology and Experimental Validation

Du, Peng; O’Grady, Greg; Davidson, John B.; Cheng, Leo K.; Pullan, Andrew J.

doi:10.1615/critrevbiomedeng.v38.i3.10

Cited by 36 publications

(31 citation statements)

References 92 publications

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“…Normal gastrointestinal motility results from the coordinated interplay of multiple cooperating mechanisms, both intrinsic and extrinsic to the gastrointestinal tract [20]. A fundamental component of this activity is an omnipresent electrical activity termed slow waves, which is generated and propagated by the ICC [20].…”

Section: Discussionmentioning

confidence: 99%

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Expression and Significance of Neuroligins in Myenteric Cells of Cajal in Hirschsprung's Disease

et al. 2013

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PurposeThe aim of this study was to investigate the expression and significance of neuroligins in myenteric cells of Cajal (ICC-MY) in Hirschsprung’s disease (HSCR).MethodsLongitudinal muscle with adherent myenteric plexus (LMMP) from surgical excision waste colon of HSCR children were prepared by peeling off the mucous layer, sub-mucosal layer and circular muscle. Neuroligins, c-Kit (c-Kit-immunoreactivity representing ICC) and their relationship were assessed by double labeling immunofluorescence staining. ICC-MY were dissociated and cultured from LMMP by enzymolysis method, and were purified and analyzed using a combination of magnetic-activated cell sorting (MACS) and flow cytometry (FCM). Western-blot analysis was applied to compare and evaluate the expression levels of neuroligins in ICC-MY which were dissociated from different segments of HSCR (ganglionic colonic segment, transitional colonic segment and aganglionic colonic segment).ResultsNeuroligins and c-Kit were expressed on the same cells (ICC-MY); ICC-MY were dissociated, cultured and purified. For HSCR, neuroligins were expressed significantly in ICC-MY from ganglionic colonic segments, moderately in those from transitional colonic segments and down-regulated significantly in those from aganglionic colonic segments.ConclusionsNeuroligins were expressed in ICC-MY of human beings, and the expression varies from different segments of HSCR. This abnormal expression might play an important role in the pathogenesis of this disease through affecting the synaptic function of ICC-MY.

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Section: Discussionmentioning

confidence: 99%

“…A fundamental component of this activity is an omnipresent electrical activity termed slow waves, which is generated and propagated by the ICC [20]. Several different classes of ICC are now described, based on their anatomical site [21].…”

Section: Discussionmentioning

confidence: 99%

Expression and Significance of Neuroligins in Myenteric Cells of Cajal in Hirschsprung's Disease

et al. 2013

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“…A number of biophysically-based ICC and SMC slow wave models have recently been developed [6]–[8]. In further recent studies, the ICC and SMC models were electrically coupled via a gap junction conductance, through which the self-excitatory slow wave activity in the ICC model initiates the slow wave activity in the SMC model (Fig.…”

Section: Cell Electrical and Electromechanical Couplingmentioning

confidence: 99%

“…Slow wave entrainment at higher spatial scales has been simulated using the bidomain equations in several studies [6], [12]. A system of two equations (3 and 4) constitute the basic bidomain model.…”

Section: Continuum Models Of Entrainmentmentioning

confidence: 99%

“…The next critical step is to link slow wave activity to motility. Electromechanical models represent an active area of research in the cardiac field, offering a prime opportunity to translate the established multi-scale continuum modeling techniques to the GI field [5], [6] - in order to understand the complex interplay of distinct cellular mechanisms and systems across large spatiotemporal scales. However, as outlined above, the unique physiology of the GI tract also necessitates novel adaptations and approaches.…”

Section: Introductionmentioning

confidence: 99%

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A Preliminary Model of Gastrointestinal Electromechanical Coupling

Poh

Lim

et al. 2011

IEEE Trans. Biomed. Eng.

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Motility in much of the gastrointestinal (GI) tract is coordinated by an electrical event known as slow waves, and several GI motility disorders are associated with slow wave arrhythmias. The GI smooth muscle cells (SMC) generate contraction, but slow waves are actively regenerated by specialized pacemaker cells called the interstitial cells of Cajal (ICC), which are coupled to the SMC. This unique electrical coupling presents an added layer of complexity to GI electromechanical models, and a major current barrier to further progress is the lack of a framework for ICC-SMC-contraction coupling. In this study, an initial framework for the electromechanical coupling was developed in a 2D model. At each solution step, the slow wave propagation was solved first and the intracellular calcium concentration in the SMC model was related to an adapted tension-extension-calcium relationship to simulate active contraction. With identification of more GI-specific constitutive laws, the ICC-SMC-contraction approach will underpin future GI electromechanical models of health and disease states.

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The IUPS Physiome Project: A Worldwide Systems Biology Initiative

O’Grady

Cheng

2011

Systems Biology and Livestock Science

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Multiscale Modeling of Gastrointestinal Electrophysiology and Experimental Validation

Cited by 36 publications

References 92 publications

Expression and Significance of Neuroligins in Myenteric Cells of Cajal in Hirschsprung's Disease

Expression and Significance of Neuroligins in Myenteric Cells of Cajal in Hirschsprung's Disease

A Preliminary Model of Gastrointestinal Electromechanical Coupling

The IUPS Physiome Project: A Worldwide Systems Biology Initiative

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