Structural characterization of interstitial cells of Cajal in myenteric plexus and muscle layers of canine colon

1990 ◽  
Vol 68 (11) ◽  
pp. 1419-1431 ◽  
Author(s):  
I. Berezin ◽  
J. D. Huizinga ◽  
E. E. Daniel

We have carried out a detailed ultrastructural study of the interstitial cells near the myenteric plexus of the canine colon and defined the structural characteristics which distinguish them from other resident non-neural cells. We have also examined the interconnections of these interstitial cells with nerves, the longitudinal muscle, and the circular muscle. In addition, we sought connections between interstitial cells of the myenteric plexus and those described earlier at the inner border of the circular muscle in proximal and distal colon. The interstitial cells of the myenteric plexus were structurally distinctive, and made gap junctions with one another and occasionally with smooth muscle. There seemed to be two subsets of these interstitial cells, one associated with the longitudinal muscle and the other with the circular muscle. Cells of both subsets were often close (≤20 nm) to nerve profiles. The interstitial cells near the longitudinal muscle layer penetrated slightly into the muscle layer, but those near the circular muscle did not and neither set contacted the other. Moveover, interstitial cells of Cajal located near the myenteric plexus were never observed to contact those at the inner border of circular muscle. The interstitial cells of Cajal at the canine colon myenteric plexus are structurally organized to provide independent pacemaking activities for the longitudinal and adjacent circular muscle. Their dense innervation suggests that they mediate neural modulation of intestinal pacemaker activities. Moreover, they lack direct contacts with the interstitial cell network at the inner border of circular muscle, which is essential for the primary pacemaking activity of circular muscle. The structural organization of interstitial cells in canine colon is consistent with their proposed role in pacemaking activity of the two muscle layers.Key words: pacemakers, neuromodulation, interstitial cells of Cajal.

2017 ◽  
Vol 27 (2) ◽  
pp. 335-344 ◽  
Author(s):  
Lingling Wang ◽  
Yu Liang ◽  
Qiusheng Chen ◽  
Nisar Ahmed ◽  
Feng Wang ◽  
...  

The interstitial cells of Cajal (ICCs) are regarded as pacemakers and are involved in neurotransmission in the gastrointestinal tract (GIT) of animals. However, limited information is available about the existence of ICCs within the GIT of ruminants. In this study, we investigated the ultrastructural characteristics and distribution of ICCs in goat abomasum using transmission electron microscopy and c-kit immunohistochemistry. Two different kinds of c-kit immunoreactive cells were observed in the abomasum. The first was identified as ICCs, which appeared to be multipolar or bipolar in shape, with some processes. These c-kit immunoreactive cells were deposited in the submucosal layer, myenteric plexus between the circular and longitudinal muscle layers, and within the longitudinal and circular muscle layers of the abomasum. The second type of cell was round in shape and was identified as mast cells, which were located in the submucosal layer as well as in the lamina propria. Ultrastructurally, ICCs were also observed as stellate or spindle-shaped cells, which were consistent in shape with our c-kit immunoreactive cells. In the cytoplasm of ICCs, numerous mitochondria, rough endoplasmic reticulum, and caveolae were detected. ICCs were located in the myenteric plexus between the longitudinal and circular muscle layers (ICC-MY), with the longitudinal and circular muscle layer was replaced as “intramuscular layers” (ICC-IM), and in the submucosal layer (ICC-SM). In addition, we found ICCs surrounding nerve fibers and smooth muscle cells, where they formed heterocellular junctions in the form of close membrane associations or gap junctions and homocellular junctions among the processes of the ICCs. In the current study, we provide the first complete characterization of ICCs within the goat abomasum and propose that ICCs might have a key role in producing contractions in the ruminant stomach for proper absorption of nutrients.


1993 ◽  
Vol 264 (1) ◽  
pp. G64-G73 ◽  
Author(s):  
L. W. Liu ◽  
L. Thuneberg ◽  
E. E. Daniel ◽  
J. D. Huizinga

The network of interstitial cells of Cajal (ICC) at the submucosal surface of the canine colon was selectively stained by incubation with 15-50 microM methylene blue for 30-45 min. The network was composed of regularly scattered ICC cell bodies interconnected by long processes. Circular muscle cells were unstained. Staining of neurons was limited to one or two axons within bundles. The ICC network had a thickness of a single cell, since no overlapping of ICC cell bodies was observed. The ICC network connected the circular muscle cells at the submucosal surface across the septa which circumferentially divided the circular muscle into lamellae. Methylene blue at 50 microM slightly decreased the resting membrane potential and increased the duration of slow waves, leading to an increase in the force of phasic contractions, with no significant influence on other slow-wave parameters. Methylene blue produced neither electrophysiological nor mechanical effects on circular muscle preparations from which the submuscular ICC network was removed, indicating that the excitatory effects of methylene blue on the full-thickness circular muscle layer were mediated by ICC. In summary, the three-dimensional aspects of the submuscular ICC network can be visualized after selective staining by methylene blue. This staining does not affect physiological characteristics of smooth muscle cells.


1998 ◽  
Vol 275 (6) ◽  
pp. G1309-G1316 ◽  
Author(s):  
Robert Hagger ◽  
Sussan Gharaie ◽  
Caroline Finlayson ◽  
Devinder Kumar

The interstitial cells of Cajal (ICC) are thought to play an important role in the control of gut motility. The regional and transmural pattern of distribution of ICC in the normal human colon and rectum was evaluated with immunohistochemistry using an anti-c- kit antibody. The transmural distribution of ICC was constant throughout the whole colon, the density of ICC was significantly greater at the myenteric plexus than at either the longitudinal or circular muscle layers, and in the rectum the transmural distribution was more even. Regionally, at the myenteric plexus, the transverse colon had a significantly greater density of ICC compared with the right colon ( P = 0.038), left colon ( P = 0.006), and rectum ( P = 0.008). The pattern of distribution of ICC identified in this study is consistent with the proposed roles of ICC as colorectal pacemakers, intermediaries of the neural control of muscle activity, and coordinators of colorectal muscle activity. The highest density of ICC was at the myenteric plexus of the transverse colon, which is the proposed region of pacemaking activity.


1997 ◽  
Vol 3 (S2) ◽  
pp. 255-256
Author(s):  
A.M.R Yunker ◽  
K.A. Roth

Interstitial cells of Cajal (ICCs) were first described as primitive neurons found within organs innervated by autonomie nerves. In the gut, ICCs are juxtaposed among enteric nerve fibers and smooth muscle cells, suggesting they may modulate enteric neurotransmission and affect motility. The recent discovery of neurokinin-1 receptor (NKrl)-like immunoreactivity (ir) on ICCs has strengthened this hypothesis. This study compared the distribution of NKlr-ir to the staining patterns of other reported markers of ICCs including cholera toxin subunit b (CTB), neuron specific enolase (NSE), NADH diaphorase, NADPH diaphorase, nitric oxide synthase (NOS), and vimentin. Albino male rats were anesthetized and whole mount preparations of myenteric plexus-longitudinal muscle with attached circular muscle were dissected. ICCs were stained using multi-label techniques and cells were visualized with a Sarastro 2000 confocal laser scanning microscope equipped with Image Space software.In the small intestine, ICCs associated with circular muscle, but not longitudinal muscle, expressed NKlr-ir.


2012 ◽  
Vol 27 (3) ◽  
pp. 244-250 ◽  
Author(s):  
Sidney Pereira Pinto Lemos ◽  
José Luiz Martins ◽  
Patrícia Veruska Ribeiro Barbosa Lemos ◽  
Silvio Romero Gonçalves e Silva ◽  
Fernando Leandro dos Santos ◽  
...  

PURPOSE: The pathophysiology of abnormalities associated with myenteric plexus lesions remains imperfectly understood. Such abnormalities have been correlated with subocclusive intestinal conditions in children with Hirschsprung's disease, cases of chronic constipation and, postoperatively, in cases of anorectal anomalies. This study evaluated abnormalities of the myenteric plexus in fetus from female rats that received ethylenethiourea. METHODS: Female rats were exposed to ethylenethiourea on the 11th day of pregnancy (experimental group) or to 0.9% physiological solution (control group). Abnormalities were only found in the experimental group. The digestive tract muscle layer was analyzed morphometrically and changes to the frequencies of nerve plexus cells and interstitial cells of Cajal were evaluated, using hematoxylin-eosin, S-100 protein, neuron-specific enolase and C-Kit, respectively. RESULTS: Muscle and skeletal abnormalities were observed in 100%, anorectal anomalies in 86%, absent tail in 71%, short tail in 29%, duodenal atresia in 5%, esophageal atresia in 5% and persistent omphalomesenteric duct in 5%. Histopathological analysis showed a thinner muscle layer associated with lower frequencies of ganglion cells and interstitial cells of Cajal, in all gastrointestinal tract. CONCLUSION: Severe nerve plexus abnormalities associated with muscle layer atrophy were observed throughout the gastrointestinal tract in newborn rats exposed to ethylenethiourea.


2001 ◽  
Vol 281 (2) ◽  
pp. G533-G543 ◽  
Author(s):  
Y. F. Wang ◽  
E. E. Daniel

In the canine gastrointestinal tract, the roles that gap junctions play in pacemaking and neurotransmission are unclear. Using antibodies to connexin (Cx)43, Cx45, and Cx40, we determined the distribution of these connexins. Cx43 was present in all locations where structural gap junctions occur. Cx40 was also widely distributed in the circular muscle of the lower esophageal sphincter (LES), stomach, and ileum. Cx45 was sparsely distributed in circular muscle of the LES. In the interstitial cells of Cajal (ICC) networks of myenteric plexus, in the deep muscular and submuscular plexuses, sparse Cx45 and Cx40 immunoreactivity was present. In colon, immunoreactivity was found only in the myenteric and submuscular plexus and nearby circular muscle cells. No immunoreactivity was found in sites lacking structural gap junctions (longitudinal muscle, inner circular muscle of the intestine, and most circular muscle of the colon). Studies of colocalization of connexins suggested that in the ICC networks, some colocalization of Cx43 with Cx40 and/or Cx45 occurred. Thus gap junctions in canine intestine may be heterotypic or heteromeric and have different conductance properties in different regions based on different connexin compositions.


1990 ◽  
Vol 68 (11) ◽  
pp. 1437-1446 ◽  
Author(s):  
M. S. Faussone-Pellegrini ◽  
C. Cortesini ◽  
D. Pantalone

The circular muscle layer of the human caecum and ascending colon is clearly subdivided into two portions: an outer one which includes the bulk of the circular muscle layer, and an inner one made up of only six to eight rows of cells. In the right transverse colon no demarcation can be observed, but a difference exists between the innermost and the outermost cells, since those of the two innermost rows possess some peculiarities with regard to the sarcoplasmic reticulum, glycogen particles, caveolae, and intercellular junctions. In the left part of the colon, the circular muscle layer is also divided into two portions. In fact, the innermost smooth muscle cells still possess peculiar morphologies, progressively increase in number, and become separate from each other making up a superficial muscle network. A fibrous lamella, along and inside which a ganglionated nerve plexus runs, is strictly apposed to the submucosal border of the circular muscle layer of the entire colonic length. A second nerve plexus runs between the two portions of the circular muscle layer. Both these plexuses are accompanied by interstitial cells of Cajal in the right colon only. The peculiar organization of the entire submucosal border of the human colonic circular muscle layer distinguishes it from other parts of the gut and probably represents a structural basis for control of human colonic motility. The presence of putative pacemaker cells (interstitial cells and peculiar smooth muscle cells) indicates that the inner border of human colonic circular muscle layer possesses pacemaking activities. Moreover, the interstitial cell – smooth muscle cell ratio differs depending on the colonic level; two main regions can be identified: the right and the left colon. Consequently, we might expect regional variation in pacemaking.Key words: smooth muscle cells, interstitial cells of Cajal, human colon, ultrastructure.


1992 ◽  
Vol 263 (2) ◽  
pp. G269-G276 ◽  
Author(s):  
J. F. Kuemmerle ◽  
G. M. Makhlouf

Opioid receptors were characterized on muscle cells isolated separately from the circular and longitudinal muscle layers of rabbit intestine. Selective radioligands for kappa- ([3H]U69,593), delta- ([3H][D-Pen2,5]enkephalin, DPDPE), and mu- ([3H][D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin, DAGO) opioid receptors were used in conjunction with a technique of receptor protection designed to enrich cells with a specific receptor type. Binding was observed only in cells from the circular muscle layer. Binding was rapid (peak within 2 min), temperature dependent, and concentration dependent. Dissociation constants (Kd) for high-affinity binding sites derived from saturation curves (1.1 +/- 0.3 nM for U69,593, 0.39 +/- 0.04 nM for DPDPE, and 1.9 +/- 0.3 nM for DAGO) were similar to Kd values derived from competition curves. In competition studies, the order of potency with which opioid ligands inhibited binding depended on the radioligand used: U69,593 (Kd 1.5 +/- 0.2 nM) inhibited preferentially the binding of [3H]U69,593, DPDPE (Kd 0.72 +/- 0.16 nM) the binding of [3H]DPDPE and DAGO (Kd 1.2 +/- 0.3 nM) the binding of [3H]DAGO. In each instance the other two ligands were 400-12,000 times less potent. In cells enriched with one receptor type, binding and contraction were observed only with the corresponding selective ligand. The potency of the ligand was slightly enhanced, whereas the potencies of the other two ligands were further reduced (greater than 10,000-fold). We conclude that distinct kappa-, delta-, and mu-opioid receptors are present on muscle cells of the circular but not longitudinal muscle layer of the intestine.


2001 ◽  
Vol 281 (5) ◽  
pp. C1727-C1733 ◽  
Author(s):  
Akikazu Fujita ◽  
Tadayoshi Takeuchi ◽  
Noriko Saitoh ◽  
Jun Hanai ◽  
Fumiaki Hata

A role for small-conductance Ca2+-activated K+ (SK) channels on spontaneous motility of the gastrointestinal tract has been suggested. Although four subtypes of SK channels were identified in mammalian tissues, the subtypes of SK channel expressed in the gastrointestinal tract are still unknown. In this study, we investigated the expression and localization of SK channels in the gastrointestinal tract. RT-PCR analysis shows expression of SK3 and SK4 mRNA, but not SK1 or SK2 mRNA, in the rat intestine. SK3 immunoreactivity was detected in the myenteric plexus and muscular layers of the stomach, ileum, and colon. SK3-immunoreactive cells were stained with antibody for c-kit, a marker for the interstitial cells of Cajal (ICC), but not with that for glial fibrillary acidic protein in the ileum and stomach. Immunoelectron microscopic analysis indicates that SK3 channels are localized on processes of ICC that are located close to the myenteric plexus between the longitudinal and circular muscle layers and within the muscular layers. Because ICC have been identified as pacemaker cells and are known to play a major role in generating the regular motility of the gastrointestinal tract, these results suggest that SK3 channels, which are expressed specifically in ICC, play an important role in generating a rhythmic pacemaker current in the gastrointestinal tract.


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