Are Interstitial Cells of Cajal Involved in Mechanical Stress-Induced Gene Expression and Impairment of Smooth Muscle Contractility in Bowel Obstruction?

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.

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

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1984.246.3.g305 ◽

1984 ◽

Vol 246 (3) ◽

pp. G305-G315 ◽

Cited By ~ 26

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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Action potentials in gastrointestinal smooth muscle

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y91-166 ◽

1991 ◽

Vol 69 (8) ◽

pp. 1133-1142 ◽

Cited By ~ 18

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.

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

AJP Cell Physiology ◽

10.1152/ajpcell.2000.279.2.c529 ◽

2000 ◽

Vol 279 (2) ◽

pp. C529-C539 ◽

Cited By ~ 131

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.

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Proteins of interstitial cells of Cajal and intestinal smooth muscle, colocalized with caveolin-1

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00222.2004 ◽

2005 ◽

Vol 288 (3) ◽

pp. G571-G585 ◽

Cited By ~ 35

Author(s):

Woo Jung Cho ◽

E. E. Daniel

Keyword(s):

Skeletal Muscle ◽

Smooth Muscle ◽

Gap Junction ◽

Interstitial Cells Of Cajal ◽

Smooth Muscles ◽

Circular Muscle ◽

Interstitial Cells ◽

Caveolin 1 ◽

Cells Of Cajal ◽

Junction Proteins

The murine jejunum and lower esophageal sphincter (LES) were examined to determine the locations of various signaling molecules and their colocalization with caveolin-1 and one another. Caveolin-1 was present in punctate sites of the plasma membranes (PM) of all smooth muscles and diffusely in all classes of interstitial cells of Cajal (ICC; identified by c-kit immunoreactivity), ICC-myenteric plexus (MP), ICC-deep muscular plexus (DMP), ICC-serosa (ICC-S), and ICC-intramuscularis (IM). In general, all ICC also contained the L-type Ca2+ (L-Ca2+) channel, the PM Ca2+ pump, and the Na+/Ca2+ exchanger-1 localized with caveolin-1. ICC in various sites also contained Ca2+-sequestering molecules such as calreticulin and calsequestrin. Calreticulin was present also in smooth muscle, frequently in the cytosol, whereas calsequestrin was present in skeletal muscle of the esophagus. Gap junction proteins connexin-43 and -40 were present in circular muscle of jejunum but not in longitudinal muscle or in LES. In some cases, these proteins were associated with ICC-DMP. The large-conductance Ca2+-activated K+ channel was present in smooth muscle and skeletal muscle of esophagus and some ICC but was not colocalized with caveolin-1. These findings suggest that all ICC have several Ca2+-handling and -sequestering molecules, although the functions of only the L-Ca2+ channel are currently known. They also suggest that gap junction proteins are located at sites where ultrastructural gap junctions are know to exist in circular muscle of intestine but not in other smooth muscles. These findings also point to the need to evaluate the function of Ca2+ sequestration in ICC.

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