interstitial cells of Cajal
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Interstitial cells of Cajal (ICC) are interstitial cells found in the
gastrointestinal tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the Digestion, digestive system that leads from the mouth to the anus. The tract is the largest of the body's systems, after the cardiovascula ...
. There are different types of ICC with different functions. ICC and another type of interstitial cell, known as platelet-derived growth factor receptor alpha (PDGFRα) cells, are electrically coupled to smooth muscle cells via
gap junction Gap junctions are membrane channels between adjacent cells that allow the direct exchange of cytoplasmic substances, such small molecules, substrates, and metabolites. Gap junctions were first described as ''close appositions'' alongside tight ...
s, that work together as an SIP functional syncytium. Myenteric interstitial cells of Cajal (ICC-MY) serve as pacemaker cells that generate the bioelectrical events known as slow waves. Slow waves conduct to smooth muscle cells and cause phasic contractions. The picture to the right shows an isolated Interstitial cell of Cajal from the Myenteric plexus of the mouse small intestine grown in a primary cell culture. This cell type can be characterized morphologically as having a small cell body often triangular or stellate-shaped with several long processes branching out into secondary and tertiary extensions - these processes often contact smooth muscle cells. They have contractile behaviour in both the cell body and the extended processes.


Embryology

These cells are derived from
mesoderm The mesoderm is the middle layer of the three germ layers that develops during gastrulation in the very early development of the embryo of most animals. The outer layer is the ectoderm, and the inner layer is the endoderm.Langman's Medical ...
, unlike the enteric neurons that arise from neural crest cells.


Function

Intramuscular Interstitial cells of Cajal (ICC-IM) are involved in mediating responses to neurotransmission. All ICC in the gastrointestinal tract express calcium-activated chloride channels encoded by the gene ''ANO1''. These channels are activated by release of calcium in ICC and are important for both the pacemaker activity of ICC and their responses to neurotransmitters. A recent review noted that
carbachol Carbachol, also known as carbamylcholine and sold under the brand name Miostat among others, is a cholinomimetic drug that binds and activates acetylcholine receptors. Thus it is classified as a cholinergic agonist. It is primarily used for v ...
increases ICC activity through this channel. ANO1-knockout mice fail to produce slow waves and ANO1 channel inhibitors block slow waves. ICC are also thought to be present in other types of smooth muscle tissues. But with few exceptions the function of these cells is not well understood and currently an area of active
research Research is creative and systematic work undertaken to increase the stock of knowledge. It involves the collection, organization, and analysis of evidence to increase understanding of a topic, characterized by a particular attentiveness to ...
.


Role in slow wave activity

ICC serve as
electrical Electricity is the set of physical phenomena associated with the presence and motion of matter possessing an electric charge. Electricity is related to magnetism, both being part of the phenomenon of electromagnetism, as described by Maxwel ...
pacemakers and generate spontaneous electrical slow waves in the gastrointestinal (GI) tract. Electrical slow waves spread from ICC to smooth muscle cells and the resulting depolarization initiates calcium ion entry and contraction. Slow waves organize gut contractions into phasic contractions that are the basis for
peristalsis Peristalsis ( , ) is a type of intestinal motility, characterized by symmetry in biology#Radial symmetry, radially symmetrical contraction and relaxation of muscles that propagate in a wave down a tube, in an wikt:anterograde, anterograde dir ...
and segmentation.


Frequency of ICC pacemaker cells

The frequency of ICC pacemaker activity differs in different regions of the GI tract: * 3 per minute in the
stomach The stomach is a muscular, hollow organ in the upper gastrointestinal tract of Human, humans and many other animals, including several invertebrates. The Ancient Greek name for the stomach is ''gaster'' which is used as ''gastric'' in medical t ...
* 11-12 per minute in the
duodenum The duodenum is the first section of the small intestine in most vertebrates, including mammals, reptiles, and birds. In mammals, it may be the principal site for iron absorption. The duodenum precedes the jejunum and ileum and is the shortest p ...
* 8-9 per minute in the
ileum The ileum () is the final section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms posterior intestine or distal intestine may ...
* 3-4 per minute in the colon ICC also mediate neural input from enteric
motor neuron A motor neuron (or motoneuron), also known as efferent neuron is a neuron whose cell body is located in the motor cortex, brainstem or the spinal cord, and whose axon (fiber) projects to the spinal cord or outside of the spinal cord to directly o ...
s. Animals lacking ICC have greatly reduced responses to the
neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a Chemical synapse, synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell. Neurotra ...
acetylcholine Acetylcholine (ACh) is an organic compound that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Par ...
, released from excitatory motor neurons, and to the
transmitter In electronics and telecommunications, a radio transmitter or just transmitter (often abbreviated as XMTR or TX in technical documents) is an electronic device which produces radio waves with an antenna (radio), antenna with the purpose of sig ...
nitric oxide Nitric oxide (nitrogen oxide, nitrogen monooxide, or nitrogen monoxide) is a colorless gas with the formula . It is one of the principal oxides of nitrogen. Nitric oxide is a free radical: it has an unpaired electron, which is sometimes den ...
, released from inhibitory motor neurons. Loss of ICC in
disease A disease is a particular abnormal condition that adversely affects the structure or function (biology), function of all or part of an organism and is not immediately due to any external injury. Diseases are often known to be medical condi ...
, therefore, may interrupt normal neural control of gastrointestinal (GI) contractions and lead to functional GI disorders, such as
irritable bowel syndrome Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterized by a group of symptoms that commonly include abdominal pain, abdominal bloating, and changes in the consistency of bowel movements. These symptoms may ...
. ICC also express mechano-sensitive mechanisms that cause these cells to respond to stretch. Stretching GI muscles can affect the
resting potential The relatively static membrane potential of quiescent cells is called the resting membrane potential (or resting voltage), as opposed to the specific dynamic electrochemical phenomena called action potential and graded membrane potential. The re ...
s of ICC and affect the frequency of pacemaker activity.
Carbachol Carbachol, also known as carbamylcholine and sold under the brand name Miostat among others, is a cholinomimetic drug that binds and activates acetylcholine receptors. Thus it is classified as a cholinergic agonist. It is primarily used for v ...
increases ICC activity through ANO1 activation. ICC are also critical in the propagation of electrical slow waves. ICC form a network through which slow wave activity can propagate. If this network is broken, then 2 regions of muscle will function independently.


Pathology

ICCs are thought to be the cells from which gastrointestinal stromal tumours (GISTs) arise. Also, abnormalities in the ICC network is one cause of chronic intestinal pseudo-obstruction.Full Text
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Eponym

The interstitial cells of Cajal are named after Santiago Ramón y Cajal, a Spanish
pathologist Pathology is the study of disease. The word ''pathology'' also refers to the study of disease in general, incorporating a wide range of biology research fields and medical practices. However, when used in the context of modern medical treatme ...
and
Nobel laureate The Nobel Prizes (, ) are awarded annually by the Royal Swedish Academy of Sciences, the Swedish Academy, the Karolinska Institutet, and the Norwegian Nobel Committee to individuals and organizations who make outstanding contributions in th ...
.


See also

*
List of human cell types derived from the germ layers This is a list of Cell (biology), cells in humans derived from the three embryonic germ layers – ectoderm, mesoderm, and endoderm. Cells derived from ectoderm Surface ectoderm Skin * Trichocyte (human), Trichocyte * Keratinocyte Anterior pi ...
* Telocyte, a similar, and potentially equivalent, cell


References


External links

{{Gastrointestinal physiology Digestive system