Fat deposition in the tunica muscularis and decrease of interstitial cells of Cajal and nNOS-positive neuronal cells in the aged rat colon

2014 ◽  
Vol 306 (8) ◽  
pp. G659-G669 ◽  
Author(s):  
Hyun Jin Jo ◽  
Nayoung Kim ◽  
Ryoung Hee Nam ◽  
Jung Mook Kang ◽  
Joo-Hyon Kim ◽  
...  

Little is known about the time course of aging on interstitial cells of Cajal (ICC) of colon. The aim of this study was to investigate the change of morphology, ICC, and neuronal nitric oxide synthase (nNOS)-immunoreactive cells in the aged rat. The proximal colon of 344 Fischer rats at four different ages (6, 31, 74 wk, and 2 yr) were studied. The immunoreactivity of c-Kit, nNOS, anti-protein gene product 9.5, and synaptophysin were counted after immunohistochemistry. The c-kit, stem cell factor (ligand of Kit), and nNOS mRNA were measured by real-time PCR. c-Kit and nNOS protein were assessed by Western blot. Isovolumetric contractile force measurement and electrical field stimulation (EFS) were conducted. The area of intramuscular fat deposition significantly increased with age after 31 wk. c-Kit-immunoreactive ICC and nNOS-immunoreactive neurons and nerve fibers significantly declined with age. mRNA and protein expression of c-kit and nNOS decreased with aging. The functional study showed that the spontaneous contractility was decreased in aged rat, whereas EFS responses in the presence of atropine and l-NG-Nitroarginine methyl ester were increased in aged rat. In conclusion, the decrease of proportion of proper smooth muscle, the density of ICC and nNOS-immunoreactive neuronal fibers, and the number of nNOS-immunoreactive neurons during the aging process may explain the aging-associated colonic dysmotility.

2003 ◽  
Vol 127 (9) ◽  
pp. 1192-1195 ◽  
Author(s):  
Anna Piaseczna Piotrowska ◽  
Valeria Solari ◽  
Prem Puri

Abstract Context.—Interstitial cells of Cajal (ICCs) are pacemaker cells in the smooth muscles of the gut. The internal anal sphincter (IAS) is the most caudal part of gastrointestinal tract. It has the important function of maintaining fecal continence. It has been proposed that ICCs in the IAS mediate the inhibitory innervation of the recto-anal reflexes. Objective.—To investigate the distribution of ICCs in the normal IAS and in the IAS of children diagnosed with internal anal sphincter achalasia (IASA) and Hirschsprung disease (HD). Methods.—At the time of IAS myectomy, specimens of the IAS were taken from 8 patients with IASA, 4 patients with HD, and 4 normal controls. All specimens were examined using anti–c-Kit and antiperipherin antibodies; immunolocalization was detected with light microscopy. Density of the ICCs was graded by computerized image analysis. Results.—There was strong peripherin immunoreactivity in the ganglia cells and nerve fibers in the normal IAS. The number of peripherin-positive nerve fibers was markedly reduced in the IAS in patients with IASA. In HD patients, there was lack of peripherin immunoreactivity in the IAS, but hypertrophic nerve trunks stained strongly. Many c-Kit–positive ICCs were present among the muscle fibers and between the muscle bundles in the normal IAS. In HD and IASA patients, ICCs were absent or markedly reduced. Conclusion.—Altered distribution of ICCs in the internal sphincter in IASA and HD may contribute to motility dysfunction in these patients.


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.


2017 ◽  
Vol 149 (7) ◽  
pp. 703-725 ◽  
Author(s):  
Bernard T. Drumm ◽  
Grant W. Hennig ◽  
Matthew J. Battersby ◽  
Erin K. Cunningham ◽  
Tae Sik Sung ◽  
...  

Interstitial cells of Cajal (ICC) in the myenteric plexus region (ICC-MY) of the small intestine are pacemakers that generate rhythmic depolarizations known as slow waves. Slow waves depend on activation of Ca2+-activated Cl− channels (ANO1) in ICC, propagate actively within networks of ICC-MY, and conduct to smooth muscle cells where they generate action potentials and phasic contractions. Thus, mechanisms of Ca2+ regulation in ICC are fundamental to the motor patterns of the bowel. Here, we characterize the nature of Ca2+ transients in ICC-MY within intact muscles, using mice expressing a genetically encoded Ca2+ sensor, GCaMP3, in ICC. Ca2+ transients in ICC-MY display a complex firing pattern caused by localized Ca2+ release events arising from multiple sites in cell somata and processes. Ca2+ transients are clustered within the time course of slow waves but fire asynchronously during these clusters. The durations of Ca2+ transient clusters (CTCs) correspond to slow wave durations (plateau phase). Simultaneous imaging and intracellular electrical recordings revealed that the upstroke depolarization of slow waves precedes clusters of Ca2+ transients. Summation of CTCs results in relatively uniform Ca2+ responses from one slow wave to another. These Ca2+ transients are caused by Ca2+ release from intracellular stores and depend on ryanodine receptors as well as amplification from IP3 receptors. Reduced extracellular Ca2+ concentrations and T-type Ca2+ channel blockers decreased the number of firing sites and firing probability of Ca2+ transients. In summary, the fundamental electrical events of small intestinal muscles generated by ICC-MY depend on asynchronous firing of Ca2+ transients from multiple intracellular release sites. These events are organized into clusters by Ca2+ influx through T-type Ca2+ channels to sustain activation of ANO1 channels and generate the plateau phase of slow waves.


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.


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