scholarly journals A novel mutation in the nucleoporin NUP35 causes murine degenerative colonic smooth muscle myopathy

2016 ◽  
Author(s):  
Ian Parish ◽  
Lincon A Stamp ◽  
Ayla May D Lorenzo ◽  
Suzanne M Fowler ◽  
Yovina Sontani ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Interstitial Cells Of Cajal ◽  
Histopathological Examination ◽  
Novel Mutation ◽  
Interstitial Cells ◽  
Enteric Neurons ◽  
Nuclear Pore ◽  
Rna Recognition Motif ◽  
Intestinal Pseudo Obstruction ◽  
Cells Of Cajal

Chronic Intestinal Pseudo-Obstruction (CIPO) is a rare, but life-threatening, disease characterized by severe intestinal dysmotility. Histopathological studies of CIPO patients have identified several different mechanisms that appear to be responsible for the dysmotility, including defects in neurons, smooth muscle or interstitial cells of Cajal. Currently there are few mouse models of the various forms of CIPO. We generated a mouse with a point mutation in the RNA Recognition Motif of the Nup35 gene, which encodes a component of the nuclear pore complex. Nup35 mutants developed a severe megacolon and exhibited reduced lifespan. Histopathological examination revealed a degenerative myopathy that developed after birth and specifically affected smooth muscle in the colon; smooth muscle in the small bowel and the bladder were not affected. Furthermore, no defects were found in enteric neurons or interstitial cells of Cajal. Nup35 mice are likely to be a valuable model for the sub-type of CIPO characterized by degenerative myopathy. Our study also raises the possibility that Nup35 polymorphisms could contribute to some cases of CIPO.

Are interstitial cells of Cajal plurifunction cells in the gut?

2008 ◽  
Vol 294 (2) ◽  
pp. G372-G390 ◽  
Author(s):  
Sushil K. Sarna
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Interstitial Cells Of Cajal ◽  
Circular Muscle ◽  
Muscle Cells ◽  
Interstitial Cells ◽  
Slow Waves ◽  
Enteric Neurons ◽  
Motility Disorders ◽  
Cells Of Cajal

The proposed functions of the interstitial cells of Cajal (ICC) are to 1) pace the slow waves and regulate their propagation, 2) mediate enteric neuronal signals to smooth muscle cells, and 3) act as mechanosensors. In addition, impairments of ICC have been implicated in diverse motility disorders. This review critically examines the available evidence for these roles and offers alternate explanations. This review suggests the following: 1) The ICC may not pace the slow waves or help in their propagation. Instead, they may help in maintaining the gradient of resting membrane potential (RMP) through the thickness of the circular muscle layer, which stabilizes the slow waves and enhances their propagation. The impairment of ICC destabilizes the slow waves, resulting in attenuation of their amplitude and impaired propagation. 2) The one-way communication between the enteric neuronal varicosities and the smooth muscle cells occurs by volume transmission, rather than by wired transmission via the ICC. 3) There are fundamental limitations for the ICC to act as mechanosensors. 4) The ICC impair in numerous motility disorders. However, a cause-and-effect relationship between ICC impairment and motility dysfunction is not established. The ICC impair readily and transform to other cell types in response to alterations in their microenvironment, which have limited effects on motility function. Concurrent investigations of the alterations in slow-wave characteristics, excitation-contraction and excitation-inhibition couplings in smooth muscle cells, neurotransmitter synthesis and release in enteric neurons, and the impairment of the ICC are required to understand the etiologies of clinical motility disorders.

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.

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.

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