scholarly journals A Close Relationship Between Networks of Interstitial Cells of Cajal and Gastrointestinal Transit In Vivo

2020 ◽  
Vol 11 ◽  
Author(s):  
Kazuhisa Kishi ◽  
Moe Kamizaki ◽  
Noriyuki Kaji ◽  
Satoshi Iino ◽  
Masatoshi Hori
Keyword(s):  
Myenteric Plexus ◽  
Immunohistochemical Staining ◽  
Interstitial Cells Of Cajal ◽  
Gastrointestinal Transit ◽  
Interstitial Cells ◽  
Pacemaker Activity ◽  
Specific Marker ◽  
Gi Transit ◽  
Cells Of Cajal

The interstitial cells of Cajal associated with the myenteric plexus (ICC-MP) are located in the same area as the myenteric plexus. ICC-MP networks are linked to the generation of electrical pacemaker activity that causes spontaneous gastrointestinal (GI) contractions; however, its role in GI transit is not clear. The aim of this study was to comprehensively investigate the effect of ICC-MP disruption on GI transit in vivo using W/Wv mice, partially ICC-deficient model mice. In this study, we measured GI transit using a 13C-octanoic acid breath test, an orally administered dye and a bead expulsion assay. ICC were detected by immunohistochemical staining for c-Kit, a specific marker for ICC. Interestingly, we found that gastric emptying in W/Wv mice was normal. We also found that the ability of small intestinal and colonic transit was significantly reduced in W/Wv mice. Immunohistochemical staining using whole-mount muscularis samples revealed that c-Kit-positive ICC-MP networks were formed in wild-type mice. In contrast, ICC-MP networks in W/Wv mice were maintained only in the gastric antrum and were significantly reduced in the ileum and colon. No significant changes were observed in the nerve structures of the myenteric plexus in W/Wv mice. These findings suggest that ICC-MP contribute to GI transit as a powerful driving function in vivo.

scholarly journals Interstitial cells of Cajal in the human fetal small bowel as shown by c-kit immunohistochemistry

Gut ◽  
1999 ◽  
Vol 44 (1) ◽  
pp. 65-71 ◽  
Author(s):  
T Wester ◽  
L Eriksson ◽  
Y Olsson ◽  
L Olsen
Keyword(s):  
Small Bowel ◽  
Myenteric Plexus ◽  
Interstitial Cells Of Cajal ◽  
Immunohistochemical Analysis ◽  
Interstitial Cells ◽  
Tyrosine Kinase Receptor ◽  
Pacemaker Activity ◽  
Complex Method ◽  
Neuronal Marker ◽  
Cells Of Cajal

BackgroundInterstitial cells of Cajal (ICCs) express the tyrosine kinase receptor c-kit, which is required for their development and spontaneous pacemaker activity in the bowel. From murine models it has been proposed that ICCs do not develop until after birth, but more recent findings indicate that c-kit is expressed early in the embryonic period. The temporal development of ICCs in the human gut remains unknown.AimTo investigate ICCs in the human fetal small bowel using c-kit immunohistochemistry.SubjectsSmall bowel specimens were obtained at post mortem examination of 16 fetuses and nine neonates, eight of whom were premature, born at gestational ages of 13 to 41 weeks, without gastrointestinal disorders.MethodsImmunohistochemical analysis was performed on material fixed in formalin and embedded in paraffin. The specimens were exposed to antibodies raised against c-kit (an ICC marker) and neurone specific enolase (a general neuronal marker). The ABC complex method was used to visualise binding of antibodies to the corresponding antigens.Resultsc-kit immunoreactive cells were visualised from 13 weeks of gestation. The immunoreactivity was mainly localised in association with the myenteric plexus. From about 17–18 weeks of gestation, the ICCs formed a layer along the myenteric plexus, whereas this layer appeared to be disrupted at 13–16 weeks of gestation.ConclusionsICCs are c-kit immunoreactive at least from a gestational age of 13 weeks in the human fetal small intestine. From 17–18 weeks of gestation until birth, they form a continuous layer around the myenteric ganglia.

scholarly journals Effects of Lubiprostone on Pacemaker Activity of Interstitial Cells of Cajal from the Mouse Colon

2014 ◽  
Vol 18 (4) ◽  
pp. 341 ◽  
Author(s):  
Han-Yi Jiao ◽  
Dong Hyun Kim ◽  
Jung Suk Ki ◽  
Kwon Ho Ryu ◽  
Seok Choi ◽  
...  
Keyword(s):  
Interstitial Cells Of Cajal ◽  
Interstitial Cells ◽  
Pacemaker Activity ◽  
Mouse Colon ◽  
Cells Of Cajal

scholarly journals Magnolia Officinalis Bark Extract Induces Depolarization of Pacemaker Potentials Through M2 and M3 Muscarinic Receptors in Cultured Murine Small Intestine Interstitial Cells of Cajal

2017 ◽  
Vol 43 (5) ◽  
pp. 1790-1802 ◽  
Author(s):  
Hyun Jung Kim ◽  
Taewon Han ◽  
Yun Tai Kim ◽  
Insuk So ◽  
Byung Joo Kim
Keyword(s):  
Receptor Antagonist ◽  
Interstitial Cells Of Cajal ◽  
Interstitial Cells ◽  
Pacemaker Potential ◽  
Pacemaker Potentials ◽  
Magnolia Officinalis ◽  
Cells Of Cajal ◽  
Gi Motility

Background: Magnolia officinalis Rehder and EH Wilson (M. officinalis) are traditional Chinese medicines widely used for gastrointestinal (GI) tract motility disorder in Asian countries. We investigated the effects of an ethanol extract of M. officinalis (MOE) on the pacemaker potentials of cultured interstitial cells of Cajal (ICCs) in vitro and its effects on GI motor functions in vivo. Methods: We isolated ICCs from small intestines, and the whole-cell patch-clamp configuration was used to record the pacemaker potentials in cultured ICCs in vitro. Both gastric emptying (GE) and intestinal transit rates (ITRs) were investigated in normal and GI motility dysfunction (GMD) mice models in vivo. Results: MOE depolarized ICC pacemaker potentials dose-dependently. Pretreatment with methoctramine (a muscarinic M2 receptor antagonist) and 4-DAMP (a muscarinic M3 receptor antagonist) inhibited the effects of MOE on the pacemaker potential relative to treatment with MOE alone. In addition, MOE depolarized pacemaker potentials after pretreatment with Y25130 (a 5-HT3 receptor antagonist), GR113808 (a 5-HT4 receptor antagonist) or SB269970 (a 5-HT7 receptor antagonist). However, pretreatment with RS39604 (a 5-HT4 receptor antagonist) blocked MOE-induced pacemaker potential depolarizations. Intracellular GDPβS inhibited MOE-induced pacemaker potential depolarization, as did pretreatment with Ca2+ free solution or thapsigargin. In normal mice, the GE and ITR values were significantly and dose-dependently increased by MOE. In loperamide-and cisplatin-induced GE delay models, MOE administration reversed the GE deficits. The ITRs of the GMD mice were significantly reduced relative to those of normal mice, which were significantly and dose-dependently reversed by MOE. Conclusion: These results suggest that MOE dose-dependently depolarizes ICCs pacemaker potentials through M2 and M3 receptors via internal and external Ca2+ regulation through G protein pathways in vitro. Moreover, MOE increased GE and ITRs in vivo in normal and GMD mouse models. Taken together, the results of this study show that MOE have the potential for development as a gastroprokinetic agent in GI motility function.

scholarly journals Effects of ATP on Pacemaker Activity of Interstitial Cells of Cajal from the Mouse Small Intestine

2018 ◽  
Vol 54 (1) ◽  
pp. 63
Author(s):  
Il Koo Park ◽  
Jin Ho Kim ◽  
Chan Guk Park ◽  
Man Yoo Kim ◽  
Shankar Prasad Parajuli ◽  
...  
Keyword(s):  
Small Intestine ◽  
Interstitial Cells Of Cajal ◽  
Interstitial Cells ◽  
Pacemaker Activity ◽  
Mouse Small Intestine ◽  
Cells Of Cajal

Action potential generation in the small intestine of W mutant mice that lack interstitial cells of Cajal

1996 ◽  
Vol 271 (3) ◽  
pp. G387-G399 ◽  
Author(s):  
J. Malysz ◽  
L. Thuneberg ◽  
H. B. Mikkelsen ◽  
J. D. Huizinga
Keyword(s):  
Small Intestine ◽  
Action Potentials ◽  
Interstitial Cells Of Cajal ◽  
Interstitial Cells ◽  
K Channel ◽  
Pacemaker Activity ◽  
Channel Blockade ◽  
Auerbach’S Plexus ◽  
Cells Of Cajal ◽  
Auerbach's Plexus

The small intestine of W/Wv mice lacks both the network of interstitial cells of Cajal (ICC), associated with Auerbach's plexus, and pacemaker activity, i.e., it does not generate slow-wave-type action potentials. The W/Wv muscle preparations showed a wide variety of electrical activities, ranging from total quiescence to generation of action potentials at regular or irregular frequency with or without periods of quiescence. The action potentials consisted of a slow component with superimposed spikes, preceded by a slowly developing depolarization and followed by a transient hyperpolarization. The action potentials were completely abolished by L-type Ca2+ channel blockers. W/Wv mice responded to K+ channel blockade (0.5 mM Ba2+ or 10 mM tetraethylammonium chloride) with effects on amplitude, frequency, rate of rise, and duration of the action potentials. In quiescent tissues from W/Wv mice, K+ channel blockade evoked the typical spikelike action potentials. Electron microscopy identified few methylene blue-positive cells in the W/Wv small intestine associated with Auerbach's plexus as individual ICC. Numbers of resident macrophage-like cells (MLC) and fibroblast-like cells (FLC) were significantly changed. Neither FLC nor MLC were part of a network nor did they form specialized junctions with neighboring cells as ICC do. Hence no cell type had replaced ICC at their normal morphological position associated with Auerbach's plexus. ICC were present in W/Wv mice at the deep muscular plexus in normal organization and numbers, indicating that they are not dependent on the Kit protein and do not take part in generation of pacemaker activity.

scholarly journals Molecular markers expressed in cultured and freshly isolated interstitial cells of Cajal

2000 ◽  
Vol 279 (2) ◽  
pp. C529-C539 ◽  
Author(s):  
Anne Epperson ◽  
William J. Hatton ◽  
Brid Callaghan ◽  
Philip Doherty ◽  
Rebecca L. Walker ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Small Intestine ◽  
Interstitial Cells Of Cajal ◽  
Expression Profiles ◽  
Interstitial Cells ◽  
Gastric Fundus ◽  
Soluble Form ◽  
Pacemaker Activity ◽  
Murine Small Intestine ◽  
Cells Of Cajal

Located within the tunica muscularis of the gastrointestinal (GI) tract are networks of cells known as interstitial cells of Cajal (ICC). ICC are critical for important basic functions of GI motility such as generation and propagation of slow-wave pacemaker activity and reception of regulatory inputs from the enteric nervous system. We have developed a novel procedure to identify and isolate individual ICC from freshly dispersed cell preparations of the murine small intestine and gastric fundus and to determine differential transcriptional expression We have compared the expression profiles of pacemaker ICC isolated from the murine small intestine (IC-MY) and ICC involved in neurotransmission from the gastric fundus (IC-IM). We have also compared expression profiles between ICC and smooth muscle cells (SMC) and between freshly isolated ICC and cultured ICC. Cultured ICC express smooth muscle myosin, whereas freshly dispersed ICC do not. All cell types express muscarinic receptor types M2and M3, neurokinin receptors NK1and NK3, and inhibitory receptor VIP-1, whereas only cultured ICC and SMC express VIP-2. Both cultured and freshly dispersed IC-IM and IC-MY express the soluble form of stem cell factor, whereas SMC from the gastric fundus express only the membrane-bound form.

Pacemaker potentials generated by interstitial cells of Cajal in the murine intestine

2005 ◽  
Vol 288 (3) ◽  
pp. C710-C720 ◽  
Author(s):  
Yoshihiko Kito ◽  
Sean M. Ward ◽  
Kenton M. Sanders
Keyword(s):  
Interstitial Cells Of Cajal ◽  
Circular Muscle ◽  
Muscle Cells ◽  
Interstitial Cells ◽  
Slow Waves ◽  
Pacemaker Activity ◽  
Dependent Manner ◽  
Plateau Potential ◽  
Pacemaker Potentials ◽  
Cells Of Cajal

Pacemaker potentials were recorded in situ from myenteric interstitial cells of Cajal (ICC-MY) in the murine small intestine. The nature of the two components of pacemaker potentials (upstroke and plateau) were investigated and compared with slow waves recorded from circular muscle cells. Pacemaker potentials and slow waves were not blocked by nifedipine (3 μM). In the presence of nifedipine, mibefradil, a voltage-dependent Ca2+ channel blocker, reduced the amplitude, frequency, and rate of rise of upstroke depolarization (d V/d tmax) of pacemaker potentials and slow waves in a dose-dependent manner (1–30 μM). Mibefradil (30 μM) changed the pattern of pacemaker potentials from rapidly rising, high-frequency events to slowly depolarizing, low-frequency events with considerable membrane noise (unitary potentials) between pacemaker potentials. Caffeine (3 mM) abolished pacemaker potentials in the presence of mibefradil. Pinacidil (10 μM), an ATP-sensitive K+ channel opener, hyperpolarized ICC-MY and increased the amplitude and d V/d tmax without affecting frequency. Pinacidil hyperpolarized smooth muscle cells and attenuated the amplitude and d V/d tmax of slow waves without affecting frequency. The effects of pinacidil were blocked by glibenclamide (10 μM). These data suggest that slow waves are electrotonic potentials driven by pacemaker potentials. The upstroke component of pacemaker potentials is due to activation of dihydropyridine-resistant Ca2+ channels, and this depolarization entrains pacemaker activity to create the plateau potential. The plateau potential may be due to summation of unitary potentials generated by individual or small groups of pacemaker units in ICC-MY. Entrainment of unitary potentials appears to depend on Ca2+ entry during upstroke depolarization.

scholarly journals Capsaicin Inhibits the Spontaneous Pacemaker Activity in Interstitial Cells of Cajal From the Small Intestine of Mouse

2010 ◽  
Vol 16 (3) ◽  
pp. 265-273 ◽  
Author(s):  
Seok Choi ◽  
Jae Myeong Sun ◽  
Pawan Kumar Shahi ◽  
Dong Chuan Zuo ◽  
Hyun Il Kim ◽  
...  
Keyword(s):  
Small Intestine ◽  
Interstitial Cells Of Cajal ◽  
Interstitial Cells ◽  
Pacemaker Activity ◽  
Cells Of Cajal

scholarly journals Intracellular Ca2+ release from endoplasmic reticulum regulates slow wave currents and pacemaker activity of interstitial cells of Cajal

2015 ◽  
Vol 308 (8) ◽  
pp. C608-C620 ◽  
Author(s):  
Mei Hong Zhu ◽  
Tae Sik Sung ◽  
Kate O'Driscoll ◽  
Sang Don Koh ◽  
Kenton M. Sanders
Keyword(s):  
Slow Wave ◽  
Interstitial Cells Of Cajal ◽  
Ryanodine Receptors ◽  
Interstitial Cells ◽  
Pacemaker Activity ◽  
Current Clamp ◽  
Anoctamin 1 ◽  
Intracellular Ca ◽  
Inward Currents ◽  
Cells Of Cajal

Interstitial cells of Cajal (ICC) provide pacemaker activity in gastrointestinal muscles that underlies segmental and peristaltic contractions. ICC generate electrical slow waves that are due to large-amplitude inward currents resulting from anoctamin 1 (ANO1) channels, which are Ca2+-activated Cl− channels. We investigated the hypothesis that the Ca2+ responsible for the stochastic activation of ANO1 channels during spontaneous transient inward currents (STICs) and synchronized activation of ANO1 channels during slow wave currents comes from intracellular Ca2+ stores. ICC, obtained from the small intestine of Kit +/copGFP mice, were studied under voltage and current clamp to determine the effects of blocking Ca2+ uptake into stores and release of Ca2+ via inositol 1,4,5-trisphosphate (IP3)-dependent and ryanodine-sensitive channels. Cyclocpiazonic acid, thapsigargin, 2-APB, and xestospongin C inhibited STICs and slow wave currents. Ryanodine and tetracaine also inhibited STICs and slow wave currents. Store-active compounds had no direct effects on ANO1 channels expressed in human embryonic kidney-293 cells. Under current clamp, store-active drugs caused significant depolarization of ICC and reduced spontaneous transient depolarizations (STDs). After block of ryanodine receptors with ryanodine and tetracaine, repolarization did not restore STDs. ANO1 expressed in ICC has limited access to cytoplasmic Ca2+ concentration, suggesting that pacemaker activity depends on Ca2+ dynamics in restricted microdomains. Our data from studies of isolated ICC differ somewhat from studies on intact muscles and suggest that release of Ca2+ from both IP3 and ryanodine receptors is important in generating pacemaker activity in ICC.

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