A case for interstitial cells of Cajal as pacemakers and mediators of neurotransmission in the gastrointestinal tract

doi:10.1053/gast.1996.v111.pm8690216

Gastroenterology

Volume 111, Issue 2, August 1996, Pages 492-515

https://doi.org/10.1053/gast.1996.v111.pm8690216 Get rights and content

Abstract

Electrical rhythmicity in gastrointestinal muscles has been studied for a century, but the pacemakers driving this phenomenon have been elusive. Anatomic studies suggest that interstitial cells of Cajal (ICC) may be pacemakers and conductors of electrical activity. ICC may also mediate neurotransmission from enteric neurons. Functional evaluations of ICC include the following. (1) Electrophysiology experiments on dissected muscle strips show that slow waves originate from specific sites. These pacemaker areas are populated by networks of ICC that make gap junctions with smooth muscle cells. Removal of pacemaker regions interferes with slow wave generation and propagation. (2) Chemicals that label ICC histochemically can damage ICC and abolish rhythmicity. (3) isolated ICC are spontaneously active, and several voltage-dependent ion channels, including a low-threshold Ca2+ conductance, are expressed. (4) ICC are innervated by enteric neurons, and they respond to neurotransmitters. ICC may produce nitric oxide and amplify inhibitory neurotransmission. (5) Some classes of ICC fall to develop in animals with mutations in c-kit or stem cell factor, the ligand for c-Kit receptors. Without ICC, electrical slow waves are absent. Many questions remain about the function of ICC, but modern technologies should now facilitate rapid progress toward determining the role of these cells in normal physiology and pathological conditions. (Gastroenterology 1996 Aug;111(2):492-515)

References (0)

Cited by (898)

Three-dimensional multi-field modelling of gastric arrhythmias and their effects on antral contractions
2023, Computers in Biology and Medicine
Citation Excerpt :
This layer enables the active contractions of the SW. A network of ICCs is located within the longitudinal and circumferential muscle layers, but also between these two layers at the myenteric plexus [39] and controls the activation of gastric contractions, for more details see Section 2.2. The outermost serosal layer is very thin, featuring no great mechanical resistance, and is therefore often neglected when modelling gastric motility.
The contraction activation of smooth muscle in the stomach wall (SW) is coordinated by slow electrical waves. The interstitial cells of Cajal (ICC), specialised pacemaker cells, initiate and propagate these slow waves. By establishing an electrically coupled network, each ICC adjusts its intrinsic pacing frequency to a single dominant frequency, to be a key aspect in modelling the electrophysiology of gastric tissue. In terms of modelling, additional fields associated with electrical activation, such as voltage-dependent calcium influx and the resulting deformation, have hardly been considered so far. Here we present a three-dimensional model of the electro-chemomechanical activation of gastric smooth muscle contractions. To reduce computational costs, an adaptive multi-scale discretisation strategy for the temporal resolution of the electric field is used. The model incorporates a biophysically based model of gastric ICC pacemaker activity that aims to simulate stable entrainment and physiological conduction velocities of the electrical slow waves. Together with the simulation of concomitant gastric contractions and the inclusion of a mechanical feedback mechanism, the model is used to study dysrhythmias of gastric slow waves induced by abnormal stretching of the antral SW. The model is able to predict the formation of stretch-induced gastric arrhythmias, such as the emergence of an ectopic pacemaker in the gastric antrum. The results show that the ectopic event is accompanied by smooth muscle contraction and, although it disrupts the normal propagation pattern of gastric slow electrical waves, it can also catalyse the process of handling indigestible materials that might otherwise injure the gastric SW.
Interoceptive influences on resting-state fMRI
2023, Advances in Resting-State Functional MRI: Methods, Interpretation, and Applications
In the resting state, the brain is not at rest but constantly receives internal stimuli from inside the body and regulates bodily states for homeostasis. Such bidirectional interactions between the brain and the body, namely the interoception, engage neural pathways, circuits, and dynamics at peripheral, brainstem, subcortical, and cortical levels. Interoception is an intrinsic source of spontaneous brain activity, driving functional connectivity between brain regions and dynamic coupling between the brain and visceral organs, such as the heart and the gut. The functional network of interoception overlaps with several canonical resting-state networks, including the salience network, cingulo-opercular network, default-mode network, cognitive control network, sensorimotor network, central autonomic network, reticular activating system, and limbic and mesolimbic systems. Through such overlaps, interoception may influence arousal and emotion; guide perception, cognition, and action; and link autonomic and central nervous systems.
The vagus nerve mediates the stomach-brain coherence in rats
2022, NeuroImage
Interactions between the brain and the stomach shape both cognitive and digestive functions. Recent human studies report spontaneous synchronization between brain activity and gastric slow waves in the resting state. However, this finding has not been replicated in any animal models. The neural pathways underlying this apparent stomach-brain synchrony is also unclear. Here, we performed functional magnetic resonance imaging while simultaneously recording body-surface gastric slow waves from anesthetized rats in the fasted vs. postprandial conditions and performed a bilateral cervical vagotomy to assess the role of the vagus nerve. The coherence between brain fMRI signals and gastric slow waves was found in a distributed “gastric network”, including subcortical and cortical regions in the sensory, motor, and limbic systems. The stomach-brain coherence was largely reduced by the bilateral vagotomy and was different between the fasted and fed states. These findings suggest that the vagus nerve mediates the spontaneous coherence between brain activity and gastric slow waves, which is likely a signature of real-time stomach-brain interactions. However, its functional significance remains to be established.
A Gastroenterologist's Approach to the Diagnosis and Management of Gastrointestinal Stromal Tumors
2022, Gastroenterology Clinics of North America
Structural Relationships between Interstitial Cells of Cajal and Smooth Muscle Cells/Nerve Fibers in the Gastric Muscularis Mucosae of Chinese Giant Salamander
2021, Microscopy and Microanalysis
Efficacy of Glycicumarin and Isoliquiritigenin in Suppressing Colonic Peristalsis in Both an Animal Model and a Clinical Trial
2024, Biological and Pharmaceutical Bulletin

View all citing articles on Scopus

View full text