Interstitial cell of Cajal

Not to be confused with Interstitial nucleus of Cajal and Horizontal cells of Cajal.
Interstitial cell of Cajal
Latin cellulae interstitiales stimulantes[1]

Anatomical terminology

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.[2][3]

Intramuscular Interstitial cells of Cajal [ICC-IM] are involved in the stimulation of smooth muscle cells, neurotransmitters act through them.[4] Certain calcium-activated chloride channels are now known to play an important role in regulating human gastrointestinal ICC, particularly the anoctamin channel ANO1.[5] A recent review noted that carbachol increases ICC activity through this channel.[5][6] ANO1-knockout mice fail to produce slow waves and ANO1 channel inhibitors in humans block slow wave production.[5]

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.[7]

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 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:[8]

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.[5][6]

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.


ICCs are thought to be the cells from which gastrointestinal stromal tumours (GISTs) arise.[9] Also, abnormalities in the ICC network is one cause of chronic intestinal pseudo-obstruction.[10]


The interstitial cells of Cajal are named after Santiago Ramón y Cajal,[11] a Spanish pathologist and Nobel laureate.


  2. Hennig GW, Spencer NJ, Jokela-Willis S, Bayguinov PO, Lee HT, Ritchie LA, Ward SM, Smith TK, Sanders KM (May 2010). "ICC-MY coordinate smooth muscle electrical and mechanical activity in the murine small intestine". Neurogastroenterol. Motil. 22 (5): e138–51. doi:10.1111/j.1365-2982.2009.01448.x. PMC 2856807Freely accessible. PMID 20059699.
  3. Sanders K, Koh S, Ward S (2006). "Interstitial cells of cajal as pacemakers in the gastrointestinal tract". Annu Rev Physiol. 68: 307–343. doi:10.1146/annurev.physiol.68.040504.094718. PMID 16460275.
  4. Kito Y (2011). "The functional role of intramuscular interstitial cells of Cajal in the stomach". J Smooth Muscle Res. 47 (2): 47–53. doi:10.1540/jsmr.47.47. PMID 21757854.
  5. 1 2 3 4 Sanders KM, Zhu MH, Britton F, Koh SD, Ward SM (February 2012). "Anoctamins and gastrointestinal smooth muscle excitability". Exp. Physiol. 97 (2): 200206. doi:10.1113/expphysiol.2011.058248. PMC 3272164Freely accessible. PMID 22002868.
  6. 1 2 Zhu MH, Sung IK, Zheng H, Sung TS, Britton FC, O'Driscoll K, Koh SD, Sanders KM (September 2011). "Muscarinic activation of Ca2+-activated Cl- current in interstitial cells of Cajal". J. Physiol. (Lond.). 589 (Pt 18): 4565–82. doi:10.1113/jphysiol.2011.211094. PMC 3208225Freely accessible. PMID 21768263.
  7. Kursad Turksen (2006). Embryonic Stem Cell Protocols: Differentiation models. Humana Press. pp. 263–. ISBN 978-1-58829-784-6. Retrieved 14 April 2010.
  8. Pocock, Richards, Richards, Human Physiology 4/ed, Oxford University Press, 2012. ISBN 978-0-19-957493-3. p.581
  9. Miettinen M, Lasota J (2006). "Gastrointestinal stromal tumors: review on morphology, molecular pathology, prognosis, and differential diagnosis". Arch Pathol Lab Med. 130 (10): 1466–78. doi:10.1043/1543-2165(2006)130[1466:GSTROM]2.0.CO;2. ISSN 1543-2165. PMID 17090188.
  10. De Giorgio R, Sarnelli G, Corinaldesi R, Stanghellini V (2004). "Advances in our understanding of the pathology of chronic intestinal pseudo-obstruction". Gut. 53 (11): 1549–1552. doi:10.1136/gut.2004.043968. PMC 1774265Freely accessible. PMID 15479666. Full Text
  11. Sanders K, Ward S (2006). "Interstitial cells of Cajal: a new perspective on smooth muscle function". J Physiol. 576 (Pt 3): 721–726. doi:10.1113/jphysiol.2006.115279. PMC 1890422Freely accessible. PMID 16873406.
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