A Model of Electromechanical Coupling in the Small Intestine - Multiscale Computer Modeling in Biomechanics and Biomedical Engineering - page 178

Nobel Prize recipient, Santiago Ramón y Cajal, in 1911 [ 11 ]. However, it took
decades before the pacemaking role of the interstitial cells of Cajal in electrome-
chanical coupling activity in the gastrointestinal tract was established [ 21 ]. The
clinical significance of interstitial cells of Cajal has been demonstrated by multiple
studies showing a strong correlation between loss of the cells and intestinal motility
disorders such as chronic intestinal pseudo-obstruction [ 22 ]. In the muscle layers of
the small intestine, the smooth muscle cells are arranged in two sheets, defined as the
circular and longitudinal layers, which refer to the principal direction of alignment
of the individual muscle cells in each layer [ 9 ]. Since two of the components
responsible for contraction, the actin and myosin filaments, are aligned roughly
parallel to the longitudinal axis of the cell body, the alignment of the cells within the
muscle layer ensures coordinated contraction and efficient force generation in the
principal direction of the layer [ 9 ].
Peristaltic motor patterns involve contraction of both the circular and longitu-
dinal muscle layers in the intestine, accomplished by voltage-mediated calcium
entry into the smooth muscle cells and calcium release from intracellular stores [ 31 ].
In addition, the electromechanical sensitivity of the smooth muscle cells is further
influenced by the resting membrane potential which varies across localised regions
as well as across the intestinal wall [ 52 ], and changes in the amount of depolarization
required to activate peristalsis in different segments of intestine. This intrinsic
control of excitability also plays an important role in the formation of many other
specific motor patterns in different physiological conditions and at different loca-
tions along the intestine.
In summary, there are multiple co-regulatory pathways imposing on the motility
of the small intestine. These pathways integrate to generate the complex contractile
patterns in response to slow wave activity in the small intestine. In this chapter, we
focus on the electromechanical coupling between the intestinal slow wave activity
and peristalsis. However, even with the current level of understanding we have of
the underlying mechanisms of peristalsis, it is still difficult to evaluate this com-
plicated response in vivo. This is where a mathematical modeling framework can
offer a highly attractive in silico environment to understand peristalsis. Here, we
present the underlying theories with simple examples of a modeling framework that
can be used to investigate the electromechanical coupling in the small intestine. The
framework offers the flexibility to modify or add new components as more infor-
mation is established. Furthermore, the output variables of the electromechanical
model are in physically meaningful quantities that can be validated experimentally.
This additionally enables the model can be used to evaluate current data, and to help
generate new hypotheses for subsequent experimental testing.
2 Geometric Modeling
The sophistication of multi-scale modeling work discussed in this chapter partly
depends on the anatomy of the small intestine. It is therefore important to first
incorporate an appropriate representation of the anatomy of intestinal tissue.