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Interstitial Cell of Cajal
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The interstitial cell of Cajal (ICC) is a type of interstitial cell found in the
gastrointestinal tract. There are different types with different functions.
Myenteric Interstitial cells of Cajal [ICC-MY] serve as a pacemaker which
creates the bioelectrical slow wave potential that leads to contraction of the
smooth muscle.
Intramuscular Interstitial cells of Cajal [ICC-IM] are involved in the stimulation
of smooth muscle cells, neurotransmitters act through them. Certain calciumactivated chloride channels are now known to play an important role in
regulating human gastrointestinal ICC, particularly the anoctamin channel
ANO1. A recent review noted that carbachol increases ICC activity through this
channel. ANO1-knockout mice fail to produce slow waves and ANO1 channel
inhibitors in humans block slow wave production.
Many types of smooth muscle tissues have now been shown to contain ICC, but
with few exceptions the function of these cells is not known and is currently an
area of active research.
These cells are derived from mesoderm.
Role in slow wave activity
ICC serve as electrical 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
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entry and contraction. Slow waves organize gut contractions into phasic
contractions that are the basis for peristalsis 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
 11-12 per minute in the duodenum
 9-10 per minute in the ileum
 3-4 per minute in the colon
ICC also mediate neural input from enteric motor neurons. Animals lacking ICC
have greatly reduced responses to the neurotransmitter acetylcholine, released
from excitatory motor neurons, and to the transmitter nitric oxide, released from
inhibitory motor neurons. Loss of ICC in disease, therefore, may interrupt
normal neural control of gastrointestinal (GI) contractions and lead to functional
GI disorders, such as irritable bowel syndrome.
ICC also express mechano-sensitive mechanisms that cause these cells to
respond to stretch. Stretching GI muscles can affect the resting potentials of
ICC and affect the frequency of pacemaker activity. Carbachol increases ICC
activity through ANO1 activation.
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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.
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