Gastrointestinal system

Abstract

The functions of the gastrointestinal (GI) tract include digestion, absorption, excretion, and protection. In this review, we focus on the electrical activity of the stomach and small intestine, which underlies the motility of these organs, and where the most detailed systems descriptions and computational models have been based to date. Much of this discussion is also applicable to the rest of the GI tract. This review covers four major spatial scales: cell, tissue, organ, and torso, and discusses the methods of investigation and the challenges associated with each. We begin by describing the origin of the electrical activity in the interstitial cells of Cajal, and its spread to smooth muscle cells. The spread of electrical activity through the stomach and small intestine is then described, followed by the resultant electrical and magnetic activity that may be recorded on the body surface. A number of common and highly symptomatic GI conditions involve abnormal electrical and/or motor activity, which are often termed functional disorders. In the last section of this review we address approaches being used to characterize and diagnose abnormalities in the electrical activity and how these might be applied in the clinical setting. The understanding of electrophysiology and motility of the GI system remains a challenging field, and the review discusses how biophysically based mathematical models can help to bridge gaps in our current knowledge, through integration of otherwise separate concepts.

FIGURE 1

Illustration of the different spatial scales of models involved in the representation of the gastrointestinal system. An anatomical torso geometry is represented at the broadest scale. An anatomical model of the human stomach is an example of the models at organ level, while at the tissue level, the different muscle layers and their cell types must be represented. At the cellular level, smooth muscle cells in the circular direction (SMC_CM) and interstitial cells of Cajal (ICC_MY) are shown. The intracellular calcium [Ca²⁺]_i signaling pathways in the Faville et al. ICC model are illustrated as an example of subcellular level models. The Faville et al ICC model states that [Ca²⁺]_i is modulated by a number of transmembrane Ca²⁺ specific ion channels, which include an inward Ca²⁺ (I_Ca), non-selective cation channel (I_SNCC), and Ca²⁺-ATPase (I_PM). In addition, [Ca²⁺]_i sequestration is also influenced at the subcellular level by the actions of the endoplasmic reticulum (ER) and mitochondria (MT).

FIGURE 2

Schematic diagram of an Interstitial Cell of Cajal (ICC) and an associated smooth muscle cell (SMC) of the circular muscle (CM) along with membrane potential (V_m) traces from an ICC and SMC. Both the ICC and SMC membrane activities demonstrate a periodicity of 3 cpm. The amplitude of the ICC membrane potential (~45 mV) is higher than that of the SMC (~34 mV). The membrane potential traces are reproduced from Ref .

FIGURE 3

Simulated gastric electrical activity (GEA) using computer-based mathematical models. Shown in (a) is simulated unitary potentials (UPs) which are believed to generate pacemaker potentials in summation, using the Faville et al. ICC model. The simulated UPs contain an autonomous frequency of 3 cpm, amplitude of 3 mV, and resting V_m of 70 mV. Shown in (b) is the simulated membrane potential (V_m) of an ICC, which is known as the pacemaker potentials, using the Aliev et al. model. The simulated pacemaker potentials contain an autonomous frequency of 3 cpm. The peak and resting membrane potential (V_m) have to be scaled in order to match experimental data, as the Aliev model is a phenomenological model. Shown in (c) are simulated pacemaker potentials using the Corrias and Buist ICC model. The simulated pacemaker potential has an autonomous frequency of 3 cpm, an amplitude of 45 mV, and a resting V_m of -70 mV. Shown in (d) is the simulated V_m of canine gastric smooth muscle cells (SMCs), which is also known as slow waves, using the Corrias and Buist SMC model. This cell model requires a pacemaker potential as an input to depolarize the V_m (an output of the SMC model). The simulated slow wave has a frequency of 3 cpm, amplitude of 35 mV, and resting V_m of -70 mV.

FIGURE 4

Schematic diagram illustrating the organization of Interstitial cells of Cajal (ICCs) and smooth muscle (SM) cells in the canine gastric antrum. SM are arranged in the longitudinal direction (LM) and the circular direction (CM) of the stomach. ICCs are distributed between the intermittent spaces of SM, which include myenteric ICCs (ICC_MY), intramuscular ICCs (ICC_IM), and septal ICCs (ICC_SEP). Also shown on the right is the representation of the ICC and SM cells in an anatomically based computational model.

FIGURE 5

Illustration of the origin and relative propagation of the gastric slow waves. The slow wave originates in the mid-corpus region on the greater curvature and rapidly spreads in a circumferential dominant manner around the stomach, as well as propagating at a slower rate down the length of the stomach..

FIGURE 6

Illustration of gastric serosal recordings using a 32-channel electrode array (E1–E32), which was placed in the orientation on a porcine stomach as shown in (a). Shown in (b) are recorded extracellular traces corresponding to eight electrodes (out of 32) with slow wave activation times marked by the red vertical lines. The locations of the red lines were determined by the most negative deflection during a slow wave event. Also shown is (c) an activation times map corresponding to the signals in (b), the isochrones of activation times indicate that slow waves propagation was in the aboral direction (E32 towards E1). Shown in (d) is a simulated slow wave event with the activation times sampled over the same dimensions as the array of electrodes (a).The activation times and direction of the simulated slow waves (d) are in a reasonable agreement with the experimental recording (c).

FIGURE 7

Anterior and sagittal views of simulated electric and magnetic fields due to a current dipole. A horizontal dipole (green arrow) in the stomach produces electric fields on the body surface (represented by the colored field; blue is negative and red is positive potential) and the magnetic field external to the body (represented by the gold arrows), with the length of the arrow indicating the strength of the magnetic field.