Location of Interstitial Cells of Cajal (ICC) in the Gastrointestinal Tract
Interstitial cells of Cajal (ICC) are primarily located in the muscularis propria of the gastrointestinal tract, with specific populations found in different layers and regions depending on their functional roles.
Distribution of ICC Throughout the GI Tract
- ICC are found throughout the gastrointestinal tract, with the highest concentration in the stomach, where they play a critical role as pacemaker cells 1
- In the small intestine, ICC are predominantly located in two distinct regions: the myenteric plexus (ICC-MY) between the circular and longitudinal muscle layers, and the deep muscular plexus (ICC-DMP) 1, 2
- In the colon, ICC are found in the myenteric region (ICC-MY), within the circular and longitudinal muscle layers (intramuscular ICC), and at the submucosal surface of the circular muscle layer 3
Specific ICC Populations and Their Locations
- ICC-MY (myenteric plexus ICC): Located between the circular and longitudinal muscle layers throughout the GI tract, particularly prominent in the stomach and small intestine 1, 3
- ICC-DMP (deep muscular plexus ICC): Found specifically in the small intestine, within the deep muscular plexus 2, 3
- ICC-IM (intramuscular ICC): Distributed within the muscle layers of the esophagus, stomach, cecum, and colon 3
- ICC-SM (submucosal ICC): Located at the submucosal surface of the circular muscle layer, particularly in the colon 3
Functional Significance of ICC Location
- ICC-MY in the stomach and small intestine function as primary pacemaker cells, generating and propagating electrical slow waves 4, 2
- ICC-DMP in the small intestine form synaptic connections with varicose nerve terminals of enteric motor neurons, mediating both cholinergic excitatory and nitrergic inhibitory neurotransmission 2
- ICC in the colon display stochastic calcium transients and can function as conditional pacemakers, requiring hyperpolarization for regenerative activity 4
Clinical Relevance of ICC Distribution
- Abnormalities in ICC distribution or density have been implicated in various gastrointestinal motility disorders 1, 5
- In gastrointestinal stromal tumors (GISTs), the most common subepithelial tumors in the GI tract, malignant transformation occurs in cells believed to originate from ICC 1
- ICC express the receptor tyrosine kinase Kit (CD117), which serves as an important immunohistochemical marker for their identification and for diagnosis of GISTs 1, 3
- Decreased ICC density has been observed in some patients with diverticulosis, suggesting a role in the pathogenesis of motility disturbances 5
Molecular Characteristics of ICC by Location
- ICC express the receptor tyrosine kinase Kit (CD117), which is essential for their development and maintenance 6, 3
- Different ICC populations show distinct gene expression profiles corresponding to their specialized functions - metabolic and calcium transport genes are upregulated in ICC-MY, while signaling proteins involved in neurotransmitter transduction are upregulated in ICC-DMP 6
- ICC express ANO1 channels that couple with calcium transients to generate electrical activity 4
Understanding the specific distribution and functions of ICC populations throughout the GI tract is essential for diagnosing and treating motility disorders and properly identifying and managing GISTs that may arise from these cells.