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Interstitial Cells of Cajal

Interstitial Cells of Cajal

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This review attempts to give a clear and concise description of the Interstitial Cells of Cajal (ICC) in both health and disease. It outlines the various important functions of the ICC as well as describing the morbidities associated with ICC dysfunction in the GIT
This review attempts to give a clear and concise description of the Interstitial Cells of Cajal (ICC) in both health and disease. It outlines the various important functions of the ICC as well as describing the morbidities associated with ICC dysfunction in the GIT

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Published by: Undergraduate Awards on Sep 01, 2012
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01/30/2014

 
Interstitial Cells of Cajal
Edward O’Connor 04433840
Fig 1: Interstitial cells of Cajal, stained and photographed by Cajal himself (left)Taken from http://discoverysedge.mayo.edu/Interstitial cells of Cajal 100 years on (right)Taken from Kito and Suzuki (2003)
 
The interstitial cells of Cajal (ICC) were discovered by the Spanish histologistSantiago Ramón y Cajal
 
over 100 years ago in the gastrointestinal tract (GIT). Theyhave numerous defining features (which apply to all the various subtypes of ICC)such as caveolae (from the Latin for 
little caves
) – invaginations of the plasmamembrane, smooth endoplasmic reticulum, profuse levels of mitochondria as well aslow resistance gap junctions with other ICC and smooth muscle cells. They arelacking thick filaments but have a large quantity of both thin and intermediatefilaments (Terumasa 2006; Huizinga
et al.
1998). There is one feature of these cells,however, that has aided research into this area enormously in recent times- this is the presence of c-kit (CD117), a cytokine receptor and proto-oncogene (a feature whichimplicates ICC in GI tumours) on the cell surface, which is easily targeted usingimmunohistochemistry. By staining tissue samples with a polyclonal anti-CD117antibody we can see the structure, location and arrangement of the ICC and their networks, thus giving us further insight into the possible functions of these cells. Kitreceptor signalling (via its ligand stem cell factor) is essential for ICC development.However, when ICC kit receptors are blocked in the pacemaker region of the smallintestine, ICC-MY, the cells do not apoptose. Instead they seem to change intosmooth muscle-like cells, developing many characteristics of the cell such as smoothmuscle myosin and desmin, but at the same time greatly decreasing the ICC population and thus abolishing pacemaker activity (see below) (Torihashi
et al.
1999).Another interesting finding in that experiment was that ICC of the deep muscular  plexus, ICC-DMP, which don’t develop until after birth, appear to remainundifferentiated when kit is blocked. This evidence suggests that kit is not onlyimportant for maintenance of the ICC phenotype, but for the differentiation of these
 
cells (ICC-blasts) into ICC-DMP. We will see later how kit and other ICCabnormalities are a major point of interest from a clinical perspective.One of the most well researched functions of the ICC is their pacemaker function, which was suggested by Keith in 1915, but ICC were only shown to berhythmically active in 1989 by Langton
et al 
. Numerous groups have observed pacemaker activity in the GIT originating in the ICC (Thomsen
et al 
1998; Huizinga
et al 
1998; Sanders 1996; Sanders
et al 
2006).
Pacemaker activity in the ICC beginswith the release of Ca
2+
from intra-cellular stores, uptake of Ca
2+
into mitochondria,and the development of small depolarizations known as unitary currents. Summationof these unitary currents (usually by cholinergic stimulation) causes depolarization(pacemaker potential) and activation of a nifedipine-resistant, nickel (primarycomponent) and DIDS (plateau component)-sensitive Ca
2+
conductance (Kito andSuzuki 2003). This slow wave conductance is spread throughout the ICC“propagation pathway” via their low resistance gap junctions with each other to thetime of a dominant pacemaker cell, contracting the GI muscle and thus facilitatingperistalsis. To break down the pacemaker potential we see that it has a rapidly risingprimary phase and a long lasting plateau phase, both of which can be inhibitedindividually. The primary phase, as mentioned above, is sensitive to nickel, indicatingthat it is T-type Ca
2+
channels causing the rapid depolarization and not L-typechannels, as experiments have been carried out using nifedipine, the results of whichso little or no effect on pacemaker potential, whilst the plateau phase is thought to be

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