Interstitial cells of Cajal (ICC) are

interstitial cells Interstitial cell refers to any cell that lies in the spaces between the functional cells of a tissue. Examples include: * Interstitial cell of Cajal (ICC) * Leydig cells, cells present in the male testes responsible for the production of androgen ...

found in the

gastrointestinal tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans and ...

. There are different types of ICC with different functions. ICC and another type of interstitial cell, known as

platelet-derived growth factor receptor alpha PDGFRA, i.e. platelet-derived growth factor receptor A, also termed PDGFRα, i.e. platelet-derived growth factor receptor α, or CD140a i.e. Cluster of Differentiation 140a, is a receptor located on the surface of a wide range of cell types. This r ...

(PDGFRα) cells, are electrically coupled to

smooth muscle cells Smooth muscle is an involuntary non-striated muscle, so-called because it has no sarcomeres and therefore no striations (''bands'' or ''stripes''). It is divided into two subgroups, single-unit and multiunit smooth muscle. Within single-unit mus ...

via

gap junction Gap junctions are specialized intercellular connections between a multitude of animal cell-types. They directly connect the cytoplasm of two cells, which allows various molecules, ions and electrical impulses to directly pass through a regula ...

s, that work together as an SIP functional syncytium.

Myenteric The myenteric plexus (or Auerbach's plexus) provides motor innervation to both layers of the muscular layer of the gut, having both parasympathetic and sympathetic input (although present ganglion cell bodies belong to parasympathetic innervation ...

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. Interstitial cell of cajal Full Picture

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. 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 var ...

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 ...

. 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 Emb ...

Role in slow wave activity

ICC serve as

electrical Electricity is the set of physical phenomena associated with the presence and motion of matter that has a property of electric charge. Electricity is related to magnetism, both being part of the phenomenon of electromagnetism, as described ...

pacemakers and generate spontaneous electrical slow waves in the gastrointestinal (GI) tract. Electrical slow waves spread from ICC to

smooth muscle cell Smooth muscle is an involuntary non-striated muscle, so-called because it has no sarcomeres and therefore no striations (''bands'' or ''stripes''). It is divided into two subgroups, single-unit and multiunit smooth muscle. Within single-unit mus ...

s 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 radially symmetrical contraction and relaxation of muscles that propagate in a wave down a tube, in an anterograde direction. Peristalsis is progression of coordinated contraction of involuntary circular muscles, whi ...

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 gastrointestinal tract of humans and many other animals, including several invertebrates. The stomach has a dilated structure and functions as a vital organ in the digestive system. The stomach i ...

* 11-12 per minute in the

duodenum The duodenum is the first 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 anterior intestine or proximal intestine m ...

* 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 m ...

* 3-4 per minute in the colon ICC also mediate neural input from

enteric The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans and ...

motor neuron A motor neuron (or motoneuron or 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 or indirect ...

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 synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell. Neu ...

acetylcholine Acetylcholine (ACh) is an organic chemical 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 is an electronic device which produces radio waves with an antenna. The transmitter itself generates a radio frequency alternating current, which is applied to the ...

nitric oxide Nitric oxide (nitrogen oxide 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 denoted by a dot in its ...

, released from

inhibitory motor neuron An inhibitory postsynaptic potential (IPSP) is a kind of synaptic potential that makes a postsynaptic neuron less likely to generate an action potential.Purves et al. Neuroscience. 4th ed. Sunderland (MA): Sinauer Associates, Incorporated; 2008. ...

s. Loss of ICC in

disease A disease is a particular abnormal condition that negatively affects the structure or function of all or part of an organism, and that is not immediately due to any external injury. Diseases are often known to be medical conditions that a ...

, therefore, may interrupt normal neural control of gastrointestinal (GI) contractions and lead to

functional GI disorder Functional may refer to: * Movements in architecture: ** Functionalism (architecture) ** Form follows function * Functional group, combination of atoms within molecules * Medical conditions without currently visible organic basis: ** Functional ...

s, such as

irritable bowel syndrome Irritable bowel syndrome (IBS) is a "disorder of gut-brain interaction" characterized by a group of symptoms that commonly include abdominal pain and or 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 A relatively static membrane potential which is usually referred to as the ground value for trans-membrane voltage. The relatively static membrane potential of quiescent cells is called the resting membrane potential (or resting voltage), as op ...

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 var ...

increases ICC activity through

ANO1 Anoctamin-1 (ANO1) also known as Transmembrane member 16A (TMEM16A) is a protein that, in humans, is encoded by the ''ANO1'' gene. Anoctamin-1 is a voltage-gated calcium-activated anion channel, which acts as a chloride channel and a bicarbonate ...

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 tumour Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. GISTs arise in the smooth muscle pacemaker interstitial cell of Cajal, or similar cells. They are defined as tumors whose behavior i ...

s (GISTs) arise. Also, abnormalities in the ICC network is one cause of

chronic intestinal pseudo-obstruction Intestinal pseudo-obstruction (IPO) is a clinical syndrome caused by severe impairment in the ability of the intestines to push food through. It is characterized by the signs and symptoms of intestinal obstruction without any lesion in the intestin ...

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Eponym

The interstitial cells of Cajal are named after

Santiago Ramón y Cajal Santiago Ramón y Cajal (; 1 May 1852 – 17 October 1934) was a Spanish neuroscientist, pathologist, and histologist specializing in neuroanatomy and the central nervous system. He and Camillo Golgi received the Nobel Prize in Physiology or M ...

, a

Spanish Spanish might refer to: * Items from or related to Spain: **Spaniards are a nation and ethnic group indigenous to Spain **Spanish language, spoken in Spain and many Latin American countries **Spanish cuisine Other places * Spanish, Ontario, Can ...

pathologist Pathology is the study of the causes and effects of disease or injury. 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 th ...

and

Nobel laureate The Nobel Prizes ( sv, Nobelpriset, no, Nobelprisen) 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 o ...

References

External links