[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: In the gastrointestinal (GI) system, motility is governed by the contraction and relaxation of smooth muscle (SM) in response
to many regulatory factors. SM in a hollow organ like stomach exhibits two types of contraction: tonic, to maintain the shape
of the organ, and phasic, in response to neurotransmitters, hormones or other signaling molecules. Motility disorders such
as dysphagia, gastroesophageal reflux disease, irritable bowel syndrome and hypotensive or hypertensive disorders all involve
abnormal SM function. Hence, it is important to gain a deeper understanding of contraction and its regulation in GI SM cells.
Skeletal muscle cells have force-velocity curves in which shortening velocities are determined only by load and the myosin
isoform. In contrast, when smooth muscle activation is altered, e.g. by changing a hormone or agonist concentration, a different
set of velocity-stress curves can be obtained. This difference is due to the regulation of both the number of active cross
bridges (determining force) and their average cycling rates (determining the velocity). The regulatory system depends on the
phosphorylation of cross-bridges, which in turn depends on cytosolic Ca2+ levels. Thus, a model has been proposed to study the effects of (a) Ca2+ concentration on the kinetics of myosin phosphorylation, (b) cross-bridge cycling rates, and (c) the latch state on tonic
and phasic contractions. The objective of the model is to describe the regulation of myosin phosphorylation and active stress
production in terms of the intracellular Ca2+ concentration. A mathematical formulation of cross bridge cycling has been adapted from the literature and the parameters
have been fitted to experimental data from GI SM. Here it was assumed that the Ca2+-calmodulin mediated phosphorylation of myosin is the primary determinant of the kinetics of cross bridge cycling. This model
is the first step towards developing a dynamic model of GI SM contraction.