Motility patterns and distribution of interstitial cells of Cajal and nitrergic neurons in the proximal, mid‐ and distal‐colon of the rat

Albertí, Elena; Mikkelsen, Hanne B.; Larsen, Jacob Norvig; Jiménez, Marcel

doi:10.1111/j.1365-2982.2004.00603.x

Cited by 64 publications

(76 citation statements)

References 36 publications

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“…2). This density is of the same order of magnitude as that reported by Alberti et al [61], who estimated the distribution of c-kit positive ICC in rat colon.…”

Section: Resultssupporting

confidence: 73%

Novel type of interstitial cell (Cajal-like) in human fallopian tube

et al. 2005

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We describe here ‐ presumably for the first time‐a Cajal‐like type of tubal interstitial cells (t‐ICC), resembling the archetypal enteric ICC. t‐ICC were demonstrated in situ and in vitro on fresh preparations (tissue cryosections and primary cell cultures) using methylene‐blue, crystal‐violet, Janus‐Green B or Mito Tracker‐Green FM Probe vital stainings. Also, t‐ICC were identified in fixed specimens by light microscopy (methylene‐blue, Giemsa, trichrome stainings, Gomori silver‐impregnation) or transmission electron microscopy (TEM). The positive diagnosis of t‐ICC was strengthened by immunohistochemistry (IHC; CD117/c‐kit+ and other 14 antigens) and immunofluorescence (IF; CD117/c‐kit+ and other 7 antigens). The spatial density of t‐ICC (ampullar‐segment cryosections) was 100–150 cells/mm2. Non‐conventional light microscopy (NCLM) of Epon semithin‐sections revealed a network‐like distribution of t‐ICC in lammina propria and smooth muscle meshwork. t‐ICC appeared located beneath of epithelium, in a 10–15μ thick ‘belt’, where 18±2% of cells were t‐ICC. In the whole lamina propria, t‐ICC were about 9%, and in muscularis ∼7%. In toto, t‐ICC represent ∼8% of subepithelial cells, as counted by NCLM. In vitro, t‐ICC were 9.9±0.9% of total cell population. TEM showed that the diagnostic ‘gold standard’ (Huizinga et al., 1997) is fulfilled by ‘our’ t‐ICC. However, we suggest a ‘platinum standard’, adding a new defining criterion ‐ characteristic cytoplasmic processes (number: 1–5; length: tens of μm; thickness: ±0.5μ; aspect: moniliform; braching: dichotomous; organization: network, labyrinthic‐system). Quantitatively, the ultrastructural architecture of t‐ICC is: nucleus, 23.6±3.2% of cell volume, with heterochromatin 49.1±3.8%; mitochondria, 4.8±1.7%; rough and smooth endoplasmic‐reticulum (1.1±0.6%, 1.0±0.2%, respectively); caveolae, 3.4±0.5%. We found more caveolae on the surface of cell processes versus cell body, as confirmed by IF for caveolins. Occasionally, the so‐called ‘Ca2+‐release units’ (subplasmalemmal close associations of caveolae+endoplasmic reticulum±mitochondria) were detected in the dilations of cell processes. Electrophysiological single unit recordings of t‐ICC in primary cultures indicated sustained spontaneous electrical activity (amplitude of field potentials: 57.26±6.56mV). Besides the CD117/c‐kit marker, t‐ICC expressed variously CD34, caveolins 1&2, α‐SMA, S‐100, vimentin, nestin, desmin, NK‐1. t‐ICC were negative for: CD68, CD1a, CD62P, NSE, GFAP, chromogranin‐A, PGP9.5, but IHC showed the possible existence of (neuro)endocrine cells in tubal interstitium. We call them ‘JF cells’. In conclusion, the identification of t‐ICC might open the door for understanding some tubal functions, e.g. pace‐making/peristaltism, secretion (auto‐, juxta‐ and/or paracrine), regulation of neurotransmission (nitrergic/purinergic) and intercellular signaling, via the very long processes. Furthermore, t‐ICC might even be uncommitted bipotential progenitor cells.

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“…2). This density is of the same order of magnitude as that reported by Alberti et al [61], who estimated the distribution of c-kit positive ICC in rat colon.…”

Section: Resultssupporting

confidence: 73%

Novel type of interstitial cell (Cajal-like) in human fallopian tube

et al. 2005

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“…34 In the normal human colon and rectum, the transverse colon has the highest density of ICCs amongst all colonic regions, as analyzed with IHC. 35 Albertí et al 33 suggested that there were no major differences in the density of KIT-positive ICCs between the AC, mid-colon, and DC in rats. However, there have been reports of normal human colons that reveal a larger population of KIT-positive cells in the DC than in the AC.…”

Section: Discussionmentioning

confidence: 99%

“…After discarding 1 cm from the cecum and anus, 5 cm of the proximal and distal parts of the colon were collected from each. 33,39 A part of each sample 1 cm in length was prepared for histological analysis by fixation in 10% buffered formalin. The tissue specimens embedded in paraffin blocks were cut perpendicularly to the lumen into 4 μm thick sections and then stained with hematoxylin and eosin.…”

Section: Tissue Preparationmentioning

confidence: 99%

“…Several studies have shown the distribution of ICCs and nNOS in the AC and DC; however, the results varied possibly because of differences in ages and species. [33][34][35][36][37] Since there is loss or scathe of ICCs and neurons in the aging colon, we hypothesized that the distribution of ICCs and nNOS may change as animals age, and the functional consequences could be different according to the colonic site. Given this background, the aim of this study is to investigate the differential distribution of ICCs and nNOS with regard to age-related changes between the AC and DC in male Fischer-344 (F344) rats.…”

Section: Introductionmentioning

confidence: 99%

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Comparison of Changes in the Interstitial Cells of Cajal and Neuronal Nitric Oxide Synthase-positive Neuronal Cells With Aging Between the Ascending and Descending Colon of F344 Rats

Lee

Kim

et al. 2017

J Neurogastroenterol Motil

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Background/AimsNeuronal degeneration and changes in interstitial cells of Cajal (ICCs) are important mechanisms of age-related constipation. This study aims to compare the distribution of ICCs and neuronal nitric oxide synthase (nNOS) with regard to age-related changes between the ascending colon (AC) and descending colon (DC) in 6-, 31-, and 74-week old and 2-year old male Fischer-344 rats. MethodsThe amount of fecal pellet and the bead expulsion times were measured. Fat proportion in the muscle layer of the colon was analyzed by hematoxylin and eosin staining. Proto-oncogene receptor tyrosine kinase (KIT) and neuronal nitric oxide synthase (nNOS) expression were analyzed with Western blotting and immunohistochemistry. Isovolumetric contractile measurements and electrical field stimulation were used to assess smooth muscle contractility. ResultsColon transit and bead expulsion slowed with senescence. Fat in the muscle layer accumulated with age in the AC, but not in the DC. The proportion of KIT-immunoreactive ICCs in the submucosal and myenteric plexus was higher in the DC than in the AC, and it declined with age, especially in the AC. In contrast, the proportion of NOS-immunoreactive neurons in the myenteric plexus was higher in the AC than in the DC, and both decreased in older rats. Nitric oxide levels declined with age in the DC. Muscle strip experiments showed that the inhibitory response mediated by nitric oxide in the circular direction of the DC was reduced in 2-year old rats. ConclusionThe AC and DC differ in their distribution of ICCs and nNOS, and age-related loss of nitrergic neurons more severely affects the DC than the AC.

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“…Intestinal smooth muscles display rhythmic spontaneous activity due to the role of interstitial cells of Cajal (ICC) as pacemaker cells in the GI tract [15][16][17][18]. Spontaneous contractions of the longitudinal muscle in the ileum and colon play an important role in GI motility, including peristalsis, and are a useful tool to investigate the regulation of motor activity.…”

Section: Introductionmentioning

confidence: 99%