Ultrastructure of interstitial cells of Cajal in the canine distal esophagus

1994 ◽  
Vol 72 (9) ◽  
pp. 1049-1059 ◽  
Author(s):  
I. Berezin ◽  
E. E. Daniel ◽  
J. D. Huizinga
Keyword(s):  
Smooth Muscle ◽  
Action Potentials ◽  
Neural Control ◽  
Interstitial Cells Of Cajal ◽  
Three Dimensional ◽  
Muscle Layer ◽  
Interstitial Cells ◽  
Distal Esophagus ◽  
Esophageal Sphincter ◽  
Cells Of Cajal

The ultrastructure of canine distal esophagus was studied focusing on interstitial cells of Cajal (ICC) and their relationships to nerves and muscle. The distal esophagus consisted of two muscle layers composed of intertwining skeletal and smooth muscle bundles. The ICC formed an interconnecting network and were an integral part of these structures. The ICC communicated with one another and with adjacent smooth muscle cells through numerous gap junctions. The morphology of individual ICC resembled that observed in other gut regions. All interstitial cells were densely innervated. The highest density of ICC, just proximal to the lower esophageal sphincter, coincided with the previously reported highest incidence of occurrence of electrical slow wave type action potentials. Examination of a large number of structural associations of ICC led us to conclude that in the distal esophagus, two networks of ICC and nerves exist, one associated with the inner muscle layer, another associated with the outer muscle layer. These networks are not sheet-like structures, such as the network of ICC in the myenteric plexus or deep muscular plexus of the small intestine, but are three dimensional and are interspersed throughout both muscle layers. The networks do not extend into Auerbach's plexus. The main branches of the networks run along the long axis of the esophagus and seem ideally suited to facilitate communication in this direction. These observations suggest that esophageal interstitial cells are structurally organized in such a manner that they may play a role in pacemaking and neural control of esophageal motility.Key words: interstitial cells of Cajal, enteric nervous system, esophagus, ultrastructure, pacemaking.

Action potentials in gastrointestinal smooth muscle

1991 ◽  
Vol 69 (8) ◽  
pp. 1133-1142 ◽  
Author(s):  
Jan D. Huizinga
Keyword(s):  
Smooth Muscle ◽  
Slow Wave ◽  
Action Potentials ◽  
Interstitial Cells Of Cajal ◽  
Cell Structure ◽  
Interstitial Cells ◽  
Research Progress ◽  
Wave Type ◽  
Gastrointestinal Smooth Muscle ◽  
Cells Of Cajal

Recent investigation of the ultrastracture and electrophysiology of gastrointestinal smooth muscle layers has revealed a fascinating heterogeneity in cell type, cell structure, intercellular communication, and generated electrical activities. Networks of interstitial cells of Cajal (ICC) have been identified in many muscle layers and evidence is accumulating for a role of these networks in gut pacemaking activity. Synchronized motility in the organs of the gut result from interaction between ICC, neural-tissue, and smooth muscle cells. Regulation of cell to cell communication between the different cell types will be an important area for further research. Progress has been made in the elucidation of the ionic basis of the slow wave type action potentials and the spike-like action potentials. The mechanism underlying smooth muscle autorhythmicity seems different from that encountered in cardiac tissue, and evidence exists for metabolic regulation of the frequency of slow wave type action potentials.Key words: pacemaker activity, slow wave, autorhythmicity, interstitial cells of Cajal.

Selective accumulation of methylene blue by interstitial cells of Cajal in canine colon

1993 ◽  
Vol 264 (1) ◽  
pp. G64-G73 ◽  
Author(s):  
L. W. Liu ◽  
L. Thuneberg ◽  
E. E. Daniel ◽  
J. D. Huizinga
Keyword(s):  
Methylene Blue ◽  
Interstitial Cells Of Cajal ◽  
Three Dimensional ◽  
Circular Muscle ◽  
Muscle Cells ◽  
Muscle Layer ◽  
Interstitial Cells ◽  
Resting Membrane Potential ◽  
Selective Staining ◽  
Cells Of Cajal

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.

Inhibitory innervation of colonic smooth muscle cells and interstitial cells of Cajal

1990 ◽  
Vol 68 (3) ◽  
pp. 447-454 ◽  
Author(s):  
Jan D. Huizinga ◽  
Irene Berezin ◽  
Edwin E. Daniel ◽  
Edwin Chow
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Action Potentials ◽  
Interstitial Cells Of Cajal ◽  
Reversal Potential ◽  
Circular Muscle ◽  
Muscle Cells ◽  
Interstitial Cells ◽  
Equilibrium Potential ◽  
Cells Of Cajal

The effect of neural inhibition on the electrical activities of circular and longitudinal colonic smooth muscle was investigated. In addition, a comparative study was carried out between circular muscle preparations with and without the "submucosal" and "myenteric plexus" network of interstitial cells of Cajal (ICC) to study innervation of the "submucosal" ICC and to investigate whether or not the ICC network is an essential intermediary system for inhibitory innervation of smooth muscle cells. Electrical stimulation of intrinsic nerves in the presence of atropine caused inhibitory junction potentials (ijps) throughout the circular and longitudinal muscle layers. The ijp amplitude depended on the membrane potential and not on the location of the muscle cells with respect to the ICC network. Neurally mediated inhibition of the colon resulted in a reduction in amplitude and duration of slow wave type action potentials in circular and abolishment of spike-like action potentials in longitudinal smooth muscle, both resulting in a reduction of contractile activity. With respect to mediation by ICC, the study shows (i) "submucosal" ICC receive direct inhibitory innervation and (ii) circular smooth muscle cells can be directly innervated by inhibitory nerves without ICC as necessary intermediaries. The reversal potential of the ijp in colonic smooth muscle was observed to be approximately −76 mV, close to the estimated potassium equilibrium potential, suggesting that the nerve-mediated hyperpolarization is caused by increased potassium conductance.Key words: enteric nerves, potassium conductance, pacemaker activity, VIP, inhibitory junction potential.

Neuromuscular structures specific to the submucosal border of the human colonic circular muscle layer

1990 ◽  
Vol 68 (11) ◽  
pp. 1437-1446 ◽  
Author(s):  
M. S. Faussone-Pellegrini ◽  
C. Cortesini ◽  
D. Pantalone
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Interstitial Cells Of Cajal ◽  
Circular Muscle ◽  
Muscle Cells ◽  
Muscle Layer ◽  
Interstitial Cells ◽  
Circular Muscle Layer ◽  
The Right ◽  
Cells Of Cajal

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.

scholarly journals Ezh2-dependent epigenetic reprogramming controls a developmental switch between modes of gastric neuromuscular regulation

2018 ◽  
Author(s):  
Sabriya A. Syed ◽  
Yujiro Hayashi ◽  
Jeong-Heon Lee ◽  
Huihuang Yan ◽  
Andrea Lorincz ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Neural Control ◽  
Interstitial Cells Of Cajal ◽  
Muscle Cells ◽  
Interstitial Cells ◽  
Pacemaker Cells ◽  
Gastric Pacemaker ◽  
Cells Of Cajal

SUMMARYPhysiological interconversion between specialized cell types has only been described in a few mammalian tissues and the mechanisms remain obscure. Using genetic lineage tracing during postnatal development and in-vitro models we demonstrate conversion of gastric interstitial cells of Cajal (ICC), regulatory cells that electrically pace phasic contractions and mediate nitrergic and cholinergic neural control of smooth muscle cells, into phenotypically distinct “fibroblast-like” interstitial cells (FLC), which only mediate purinergic signaling. Mechanistically, we find this transition to be epigenetically governed by H3K27 trimethylation of cell identity-related promoters whose susceptibility to repression is predicted by H3K27 acetylation patterns in ICC. The phenotypic switch was reversible by inhibition, knockdown or in-vivo genomic inactivation of the polycomb H3K27 methyl-transferase Ezh2. These results demonstrate a role for Ezh2-mediated epigenetic repression in physiological mammalian transdifferentiation and identify FLC as a reserve from which ICC can potentially be restored in common gastrointestinal disorders where ICC are depleted.GRAPHICAL ABSTRACTHIGHLIGHTSGastric pacemaker cells (ICC) transdifferentiate into quiescent cells (FLC) in vivoICC-to-FLC shift switches neural control from nitrergic/cholinergic to purinergicEzh2-mediated H3K27me3 represses cell-identity genes during ICC-to-FLC transitionEzh2 inhibition restores ICC numbers, phenotype and functioneTOC BLURBSyed et al. find aging to cause transdifferentiation of gastric pacemaker cells (interstitial cells of Cajal, ICC), which also communicate cholinergic and nitrergic neurotransmission to smooth muscle cells, into quiescent “fibroblast-like cells” (FLC), which only mediate purinergic signals. This switch is governed by Ezh2, whose inhibition can reverse ICC depletion.

Canine colonic circular muscle generates action potentials without the pacemaker component

1994 ◽  
Vol 72 (1) ◽  
pp. 70-81 ◽  
Author(s):  
Louis W. C. Liu ◽  
Jan D. Huizinga
Keyword(s):  
Smooth Muscle ◽  
Calcium Channel ◽  
Action Potentials ◽  
Interstitial Cells Of Cajal ◽  
Longitudinal Muscle ◽  
Circular Muscle ◽  
Muscle Cells ◽  
Interstitial Cells ◽  
Slow Waves ◽  
Cells Of Cajal

Two dominant types of action potentials in canine colon are slow wave type action potentials (slow waves) and spike-like action potentials (SLAPs). The slow waves, originating at the submuscular surface where a network of interstitial cells of Cajal (ICCs) is found, possess a pacemaker component. Activation of the pacemaker component is insensitive to voltage changes and L-type calcium channel blockers, and is postulated to involve a metabolic clock sensitive to cyclic AMP. SLAPs are more prominent in the longitudinal muscle. To understand the contribution circular muscle cells make to the generation of these action potentials, a circular muscle preparation (devoid of the submuscular ICC – smooth muscle network, longitudinal muscle, and myenteric plexus) was developed. Circular muscle preparations were spontaneously quiescent, with a resting membrane potential of −62.9 ± 0.6 mV. Ba2+ (0.5 mM) depolarized the cells to −51.8 ± 0.6 mV and induced electrical oscillations with a frequency, duration, amplitude, and rate of rise equal to 6.6 ± 0.4 cpm, 2.2 ± 0.2 s, 19.4 ± 0.9 mV, and 21.8 ± 1.7 mV/s, respectively. In most cases, Ba2+-induced oscillations were preceded by a prepotential of 4.4 ± 0.3 mV, with a rate of rise of 1.1 ± 0.1 mV/s. Ba2+-induced oscillations were abolished by 1 μM D600 as well as by repolarization of 6–12 mV. Addition of 0.1 μM Bay K8644 in the presence of Ba2+ further depolarized circular muscle cells to −42.4 ± 0.8 mV and increased the oscillation frequency to 16.8 ± 1.8 cpm. The electrical oscillations induced in circular muscle preparations by Ba2+ and Bay K8644 were similar to the SLAPs exhibited by the isolated longitudinal muscle layer, indicating that generation of SLAPs is an intrinsic property of smooth muscle cells. Forskolin (1 μM), previously shown to dramatically decrease the frequency but not the amplitude of slow waves in preparations including the submuscular ICC network, decreased the amplitude of the Ba2+-induced oscillations in circular muscle preparations without changing the frequency. These results provide strong evidence for the hypothesis that the submuscular ICC – smooth muscle network is essential for the initiation of the pacemaker component of the colonic slow waves. The mechanism for regulating the frequency of slow waves is different from that responsible for the Ba2+-induced oscillations in circular muscle preparations. Circular muscle cells are shown to be excitable and capable of generating oscillatory activity dominated by L-type calcium channel activity, which is regulated by K+ conductance.Key words: interstitial cells of Cajal, smooth muscle, dog colon, barium chloride, potassium conductance, Bay K8644, pacemaking activity.

Morphology of the canine pyloric sphincter in relation to function

1989 ◽  
Vol 67 (12) ◽  
pp. 1560-1573 ◽  
Author(s):  
E. E. Daniel ◽  
I. Berezin ◽  
H. D. Allescher ◽  
H. Manaka ◽  
V. Posey-Daniel
Keyword(s):  
Smooth Muscle ◽  
Substance P ◽  
Smooth Muscle Cells ◽  
Gap Junctions ◽  
Vasoactive Intestinal Polypeptide ◽  
Interstitial Cells Of Cajal ◽  
Circular Muscle ◽  
Interstitial Cells ◽  
Pyloric Sphincter ◽  
Cells Of Cajal

The ultrastructure and immunocytochemistry of the canine distal pyloric muscle loop, the pyloric sphincter, were studied. Cells in this muscle were connected by gap junctions, fewer than in the antrum or corpus. The sphincter had a dense innervation and a sparse population of interstitial cells of Cajal. Most such cells were of the circular muscle type but a few were of the type in the myenteric plexus. Nerves were sometimes associated with interstitial cell profiles, but most nerves were neither close to nor associated with interstitial cells nor close to smooth muscle cells. Nerve profiles were characterized by an unusually high proportion of varicosities with a majority or a high proportion of large granular vesicles. Many of these were shown to contain material immunoreactive for vasoactive intestinal polypeptide (VIP) and some had substance P (SP) immunoreactive material. All were presumed to be peptidergic. VIP was present in a higher concentration in this muscle than in adjacent antral or duodenal circular muscle. Interstitial cells of Cajal made gap junctions to smooth muscle and to one another and might provide myogenic pacemaking activity for this muscle, but there was no evidence of a close or special relationship between nerves with VIP or SP and these cells. The absence of close relationships between nerves and either interstitial cells or smooth muscle cells leaves unanswered questions about the structural basis for previous observations of discrete excitatory responses or pyloric sphincter to single stimuli or nerves up to one per second. In conclusion, the structural observations suggest that this muscle has special neural and myogenic control systems and that interstitial cells may function to control myogenic activity of this muscle but not to mediate neural signals.Key words: vasoactive intestinal polypeptide, interstitial cells of Cajal, neuropeptides, gap junctions, substance P.

Neuromuscular structures in opossum esophagus: role of interstitial cells of Cajal

1984 ◽  
Vol 246 (3) ◽  
pp. G305-G315 ◽  
Author(s):  
E. E. Daniel ◽  
V. Posey-Daniel
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Interstitial Cells Of Cajal ◽  
Circular Muscle ◽  
Muscle Cells ◽  
Interstitial Cells ◽  
Complete Relaxation ◽  
Granular Vesicles ◽  
Cells Of Cajal

The structures of the lower esophageal sphincter (LES) and body circular muscle (BCM) from opossum were compared as to neural and muscular structures and the structural relations of interstitial cells of Cajal to nerves and muscle cells. Both LES and BCM were densely innervated by nerves with varicosities containing many small agranular vesicles and a few large granular vesicles. These nerves were more closely related structurally to the interstitial cells of Cajal than to smooth muscle cells. More gap junctions were observed between smooth muscle cells and between interstitial cells of Cajal and smooth muscle cells in BCM than in LES. Those between smooth muscle cells were larger in BCM. Complete relaxation of the LES strip by isoproterenol reduced these differences but did not eliminate them. The finding that interstitial cells of Cajal often had gap-junction contacts to smooth muscle and close associations with nerves is consistent with the hypothesis that interstitial cells are intercalated between the nerves and muscles and may mediate nerve responses. These findings also suggest that LES muscle cells may be less well coupled electrically than BCM muscle cells.

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