Role of interstitial cells of Cajal in neural control of gastrointestinal smooth muscles

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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Distribution of Interstitial Cells of Cajal in the Internal Anal Sphincter of Patients With Internal Anal Sphincter Achalasia and Hirschsprung Disease

Archives of Pathology & Laboratory Medicine ◽

10.5858/2003-127-1192-doicoc ◽

2003 ◽

Vol 127 (9) ◽

pp. 1192-1195 ◽

Cited By ~ 1

Author(s):

Anna Piaseczna Piotrowska ◽

Valeria Solari ◽

Prem Puri

Keyword(s):

Anal Sphincter ◽

Internal Anal Sphincter ◽

Interstitial Cells Of Cajal ◽

Internal Sphincter ◽

Smooth Muscles ◽

Hirschsprung Disease ◽

Interstitial Cells ◽

Nerve Fibers ◽

Internal Anal Sphincter Achalasia ◽

Cells Of Cajal

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.

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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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Role of Interstitial Cells of Cajal in Motility Disorders of the Bowel

The American Journal of Gastroenterology ◽

10.1111/j.1572-0241.2003.07295.x ◽

2003 ◽

Vol 98 (3) ◽

pp. 618-624 ◽

Cited By ~ 74

Author(s):

Dhanpat Jain ◽

Khalid Moussa ◽

Manish Tandon ◽

Joan Culpepper-Morgan ◽

Deborah D. Proctor

Keyword(s):

Interstitial Cells Of Cajal ◽

Interstitial Cells ◽

Motility Disorders ◽

Cells Of Cajal

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The presence and role of interstitial cells of Cajal in the proximal intestine of shorthorn sculpin (Myoxocephalus scorpius)

Journal of Experimental Biology ◽

10.1242/jeb.141523 ◽

2016 ◽

Vol 220 (3) ◽

pp. 347-357 ◽

Cited By ~ 5

Author(s):

Jeroen Brijs ◽

Grant W. Hennig ◽

Anna-Maria Kellermann ◽

Michael Axelsson ◽

Catharina Olsson

Keyword(s):

Interstitial Cells Of Cajal ◽

Interstitial Cells ◽

Shorthorn Sculpin ◽

Myoxocephalus Scorpius ◽

Proximal Intestine ◽

Cells Of Cajal

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Local presentation of Steel factor increases expression of c-kit immunoreactive interstitial cells of Cajal in culture

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00093.2002 ◽

2003 ◽

Vol 284 (2) ◽

pp. G313-G320 ◽

Cited By ~ 50

Author(s):

Adam Rich ◽

Steven M. Miller ◽

Simon J. Gibbons ◽

John Malysz ◽

Joseph H. Szurszewski ◽

...

Keyword(s):

Interstitial Cells Of Cajal ◽

Fibroblast Cell ◽

Interstitial Cells ◽

Culture Conditions ◽

Physical Separation ◽

Steel Factor ◽

Membrane Bound ◽

Cells Of Cajal ◽

Cell Culture Conditions

The binding of Steel factor (SF) to c-kit initiates a signaling pathway essential for development and maintenance of interstitial cells of Cajal (ICC). Soluble and membrane-bound isoforms of SF are expressed in the gastrointestinal tract, but the role for either isoform in supporting ICC development is unknown. The aim of this study was to determine the role of SF in supporting ICC in culture. ICC were cultured from dissociated mouse jejunum and grown with fibroblast cell lines that produced either soluble, membrane-bound or membrane-restricted SF. ICC were identified and counted by c-kit immunoreactivity. The number of c-kit immunoreactive cells was greater in the coculture system compared with cultures grown without SF-producing fibroblasts. All forms of SF-producing fibroblasts increased ICC number in culture but physical separation of the fibroblasts from the c-kit immunoreactive cells, the addition of exogenous SF to the culture medium, or fibroblast-conditioned media did not. These results are consistent with the hypothesis that the membrane-bound form of SF preferentially contributes to expression of c-kit-positive ICC under cell culture conditions.

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