A Model of Electromechanical Coupling in the Small Intestine - Multiscale Computer Modeling in Biomechanics and Biomedical Engineering - page 186

propagation in the circular direction was assumed to be instantaneous, so that all
the points at the same axial location were activated simultaneously.

4 Electromechanical Coupling

The tension generated in intestinal smooth muscle tissue can be classified into
passive and active components. Passive tension, or ''tone'', is mainly attributed to
extracellular connective tissue opposing stretch in the muscle tissue [ 39 ]. Active
tension is generated by the intracellular mechanisms the intestinal smooth muscle
cells that are responsible for contractions. Active contractions can be further
classified as either ''tonic contractions'', which maintain the steady-state force
over long periods of time and generate ''specific tone'' in the tissue [ 26 ], or
''phasic contractions'', which are characterized by a rise in developed tension
followed by relaxation [ 39 ]. Multiple phasic contractions may also fuse together,
generating ''tetanic tone'' in the intestinal tissue [ 26 ].
During periods of contraction, the myosin units the smooth muscle cells are
phosphorylated [ 49 ]. The activation allows interaction between actin and myosin
elements in the cell. These interactions are regulated by intracellular Ca 2 þ ,so
initiation of contraction requires an increase in the [Ca 2 þ ] i . This increase in
[Ca 2 þ ] i can be induced by multiple factors, but under normal physiological con-
ditions, electromechanical coupling is widely considered as the predominant
mechanism [ 44 , 49 ]. Slow wave activation of the smooth muscle cell depolarizes
the membrane potential, and this depolarization leads to an increase in the influx of
Ca 2 þ through voltage-gated Ca 2 þ membrane channels, e.g., I LVA and I Ltype . Nor-
mally, the increase in [Ca 2 þ ] i triggers release of more Ca 2 þ from intracellular
Ca 2 þ stores in the smooth muscle cell, e.g., the sarcoplasmic reticulum.
The next step in smooth muscle contraction is the binding of intracellular Ca 2 þ to
calmodulin. There are four Ca 2 þ binding sites on calmodulin; at least three need to
be filled before the Ca 2 þ -calmodulin complex is able to activate myosin-light-chain-
kinase [ 33 ]. This partially explains the requirement for a high level of [Ca 2 þ ] i for
activating contraction. Myosin-light-chain-kinase catalyses the phosphorylation of
the light chain subunit in myosin, allowing myosin cross-bridges to attach to actin.
This process of activating cross-bridges through a phosphorylation switch is one of
the major differences between striated and smooth muscle (in striated muscle, Ca 2 þ
removes the inhibition of actin-myosin interaction instead [ 39 ]).
This section presents the principal theory and modeling technique used to
simulate electromechanical coupling in the small intestine. Figure 4 summarizes
the simulation process and highlights the main components of the electrome-
chanical model, which are individually discussed in the following subsections. In
brief, an anatomical model (Fig. 1 b) was created and the initial timing of the
electrical activation specified to match slow wave propagation velocity.