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Interstitial cells of Cajal (ICC) are responsible for the spontaneous and omnipresent electrical activity in the stomach. A quantitative description of the intracellular processes whose coordinated activity is believed to generate electrical slow waves has been developed and is presented here. In line with recent experimental evidence, the model describes how the interplay between the mitochondria and the endoplasmic reticulum in cycling intracellular [Ca.sup.2+] provides the primary regulatory signal for the initiation of the slow wave. The major ion channels that have been identified as influencing slow wave activity have been modeled according to data obtained from isolated ICC. The model has been validated by comparing the simulated profile of the slow waves with experimental recordings and shows good correspondence in terms of frequency, amplitude, and shape in both control and pharmacologically altered conditions. interstitial cells of Cajal; mathematical model; gastric electrophysiology

Experimental results have been published that report marked changes in measured epicardial potentials when the conductivity of the material surrounding the heart is altered. These reports raise a question as to the validity of the traditional two step, equivalent cardiac source approach to modeling the forward problem of electrocardiology as the equivalent source calculation occurs in what is effectively an isolated cardiac region. In the physical situation the heart is surrounded by a torso that contains many different tissue types with different conductivities and is certainly not isolated. Here, a fully coupled model of the problem is employed where the electrical pathways are continuous from a cellular level through to the body surface. This model is used to investigate the effects that torso inhomogeneities have on epicardial and body surface potentials, including comparisons with a traditional two step approach. In particular, it is shown that adding lungs changes the epicardial potentials by 17%, which is consistent with the reported experimental results. In none of the tested situations did the equivalent source approach completely reproduce the fully coupled results, supporting the notion that a fully coupled approach is required to properly solve the forward problem of electrocardiology. Index Terms--Boundary element, coupled bidomain, finite difference, finite element, forward problem.

Gastrointestinal (GI) motility is coordinated by several cooperating mechanisms, including electrical slow wave activity, the enteric nervous system (ENS), and other factors. Slow waves generated in interstitial cells of Cajal (ICC) depolarize smooth muscle cells (SMC), generating basic GI contractions. This unique electrical coupling presents an added layer of complexity to GI electromechanical models, and a 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 2-D model. At each solution step, the slow wave propagation was solved first and [\Ca^2+]_i in the SMC model was related to a \Ca^2+-tension–extension relationship to simulate active contraction. With identification of more GI-specific constitutive laws and material parameters, the ICC-SMC-contraction approach may underpin future GI electromechanical models of health and disease states. [ABSTRACT FROM AUTHOR]

A mathematical model to describe the relationship between the intracellular Ca concentration and active force production in a gastrointestinal (GI) smooth muscle cell (SMC) has been developed. Here the model has been constructed in terms of two modules, the first describing the activation of myosin light chain kinase (MLCK) through its interactions with calmodulin and Ca ions, and the second consisting of a four state scheme describing myosin phosphorylation and cross-bridge formation between actin and myosin. A prescribed Ca transient, representing the dynamic changes in intracellular free Ca that accompanies GI SMC excitation, was used as the input signal. Simulations demonstrated that at physiological Ca levels, a 33% increase in peak Ca concentration resulted in a 93% increase in myosin phosphorylation. This can possibly be attributed to the steep relationship between Ca and MLCK activation over the normal Ca range. The total number of cross-bridges (sum of cycling cross-bridges and latch-bridges) was used to predict the active force generated in response to a phasic Ca signal. The predicted forces were in qualitative agreement with experimental data from a canine antral smooth muscle strip. The development of this model represents a first step towards a greater understanding of the mechanisms that underlie GI motility. Copyright © 2010 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

One of the major aims of the International Union of Physiological Sciences (IUPS) Physiome Project is to develop multiscale mathematical and computer models that can be used to help understand human health. We present here a small facet of this broad plan that applies to the gastrointestinal system. Specifically, we present an anatomically and physiologically based modelling framework that is capable of simulating normal and pathological electrical activity within the stomach and small intestine. The continuum models used within this framework have been created using anatomical information derived from common medical imaging modalities and data from the Visible Human Project. These models explicitly incorporate the various smooth muscle layers and networks of interstitial cells of Cajal (ICC) that are known to exist within the walls of the stomach and small bowel. Electrical activity within individual ICCs and smooth muscle cells is simulated using a previously published simplified representation of the cell level electrical activity. This simulated cell level activity is incorporated into a bidomain representation of the tissue, allowing electrical activity of the entire stomach or intestine to be simulated in the anatomically derived models. This electrical modelling framework successfully replicates many of the qualitative features of the slow wave activity within the stomach and intestine and has also been used to investigate activity associated with functional uncoupling of the stomach.