Methods for Investigating the Regulation of Smooth Muscle Excitability by Interstitial Cells

2018 ◽  
pp. 305-321
Author(s):  
Bernard T. Drumm ◽  
Kenton M. Sanders
Keyword(s):  
Smooth Muscle ◽  
Interstitial Cells ◽  
Muscle Excitability

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.

Dendritic Interstitial and Myofibroblastic Cells at the Border of Salivary Gland Tumors

2001 ◽  
Vol 125 (2) ◽  
pp. 232-236
Author(s):  
Lori Soma ◽  
Virginia A. LiVolsi ◽  
Zubair W. Baloch
Keyword(s):  
Smooth Muscle ◽  
Salivary Gland ◽  
Malignant Tumors ◽  
Smooth Muscle Actin ◽  
Staining Intensity ◽  
Interstitial Cells ◽  
Salivary Gland Tumors ◽  
Benign Tumors ◽  
Low Grade ◽  
Muscle Actin

Abstract Objective.—CD34-positive dendritic interstitial cells may be associated with the regulation of tumor growth. This association has been studied in various human neoplasms, especially skin tumors. In this study, we evaluated the distribution of dendritic interstitial cells and myofibroblastic cells at the tumor periphery of various benign and malignant salivary gland neoplasms. Methods.—Forty-nine cases of salivary gland tumors were selected: 16 pleomorphic adenomas, 12 Warthin tumors, 8 polymorphous low-grade tumors, 5 adenoid cystic carcinomas, 6 acinic cell carcinomas, and 2 mucoepidermoid carcinomas. Immunohistochemical analysis was performed by using antibodies for CD34 (dendritic cells) and α-smooth muscle actin (myofibroblast) on formalin-fixed, paraffin-embedded archival tissue. Staining intensity was graded as marked (3+), moderate (2+), weak (1+), and absent (0). Results.—Staining intensity for CD34 was 3+ in 24 (86%) of 28 benign tumors (pleomorphic adenomas and Warthin tumors) and 6 (29%) of 21 malignant tumors (polymorphous low-grade tumors, acinic cell carcinomas, adenoid cystic carcinomas, and mucoepidermoid carcinomas) and 2+ in 4 (19%) of 21 malignant tumors. None of the benign tumors displayed 2+ staining with CD34. Three (11%) of 28 benign and 11 (52%) of 21 of malignant tumors failed to stain with CD34. α-Smooth muscle actin staining was 3+ in 10 (36%) of 28 benign tumors and 6 (29%) of 21 malignant tumors, and 2+ in 11 (39%) of 28 benign and 2 (9%) of 21 malignant tumors. Five (18%) of 28 benign and 11 (52%) of 21 malignant tumors failed to stain with α-smooth muscle actin. Conclusion.—We conclude that the dendritic interstitial cells and myofibroblastic cells may be associated with the regulation of tumor growth in salivary gland tumors.

Abstract 319: Tnf-α and Il-1β Decrease Myofibroblast Differentiation in 3d-cultured Mitral Valve Interstitial Cells

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Amadeus Zhu ◽  
Jane Grande-Allen
Keyword(s):  
Smooth Muscle ◽  
Mitral Valve ◽  
Heart Valve ◽  
Interstitial Cells ◽  
Valve Disease ◽  
Tissue Type ◽  
Heart Valve Diseases ◽  
Valve Interstitial Cells ◽  
Tnf Α ◽  
Valve Diseases

Background: Fibrosis contributes to many heart valve diseases such as calcific aortic valve disease, rheumatic heart disease, and secondary mitral regurgitation. Heart valve leaflets are populated by quiescent, fibroblast-like valve interstitial cells (VICs). During fibrosis, VICs differentiate into activated, myofibroblast-like cells that adversely remodel the extracellular matrix. Activated VICs overexpress α-smooth muscle actin (ACTA2/αSMA) and smooth muscle 22-α (TAGLN/SM22α) and display increased contractility. Tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β) have been reported to either promote or inhibit fibrosis, depending on tissue type. Understanding how TNF-α and IL-1β affect VIC activation in the mitral valve of the heart could enable development of pharmaceutical treatments for heart valve diseases, which are currently managed surgically. Methods: To avoid artifactual activation on tissue culture plastic, VICs were encapsulated in biomimetic scaffolds consisting of polyethylene glycol (4% w/v) functionalized with protease-degradable (GGGPQGIWGQGK) and integrin-binding (RGDS) peptides. These 3D cultures were treated with 10 ng/ml TNF-α, 10 ng/ml IL-1β, or vehicle for 2 days in low-serum (1%) media. RNA and protein were measured via qRT-PCR, western blotting, and immunostaining. To measure contractility, VICs were encapsulated in collagen I (2.5 mg/ml) gels and allowed to contract freely for 2 days. Results: TNF-α and IL-1β significantly decreased RNA expression of ACTA2 (TNF-α: -91±6%, IL-1β: -99±1% change vs. vehicle) and TAGLN (TNF-α: -77±9%, IL-1β: -93±1% change). TNF-α and IL-1β also significantly decreased αSMA protein expression (TNF-α: -76±11%, IL-1β: -91±5% change) and the percentage of αSMA-positive cells (vehicle: 21±3%, TNF-α: 13±2%, IL-1β: 13±5% positive). Finally, TNF-α and IL-1β attenuated VIC-mediated collagen gel contraction (vehicle: 81±7%, TNF-α: 71±3%, IL-1β: 61±4% contraction). Conclusions: TNF-α and IL-1β decrease VIC activation in a 3D culture model of the mitral valve. These results reveal novel pathway targets for reducing fibrosis during mitral valve disease. Future work will use this model to study the downstream signaling events that drive VIC de-activation.

Tachygastrias

2003 ◽  
Keyword(s):  
Smooth Muscle ◽  
Healthy Subjects ◽  
Interstitial Cells ◽  
Enteric Neurons ◽  
Type I ◽  
Gastric Myoelectrical Activity ◽  
Myoelectrical Activity ◽  
Circular Smooth Muscle ◽  
Gastric Dysrhythmias ◽  
System Input

Gastric dysrhythmias are abnormal myoelectrical signals originating from the stomach. As recorded from cutaneous or serosal electrodes, bradygastrias range from 0 to 2.5 cycles per minute (cpm). Bradygastrias and mixed gastric dysrhythmias are reviewed in detail in Chapter 8. Tachygastrias range from 3.75 to l0.0cpm. The normal duodenal pacesetter potential ranges from 12 to 14 cpm. In this chapter, tachygastrias are reviewed in detail. Multiple metabolic mechanisms and neural-hormonal pathways influence gastric myoelectrical activity. The normal activities of enteric neurons, smooth muscle, hormones, and extrinsic nerves influence the ongoing activity of the interstitial cells of Cajal (ICCs), the pacemaker cells of the stomach. In healthy subjects, the frequency of gastric myoelectrical activity may vary from approximately 2.5 to 3.7cpm, depending on specific circumstances or provocative tests (Fig. 7.1). Specific diseases and disorders, with their specific pathophysiologies, may adversely affect gastric myoelectrical activity and are associated with gastric dysrhythmias. For example, many patients with type I and II diabetes have gastric dysrhythmias, and in healthy subjects, hyperglycemia itself produces gastric dysrhythmias. Gastric dysrhythmias occur when the ICCs are damaged or dysfunctional or when enteric neurons, circular smooth muscle cells (and perhaps longitudinal muscle activity), and extrinsic nerve activity from the parasympathetic and sympathetic nervous system input to the stomach are abnormal. Endocrine, neurocrine, and paracrine activities may also affect interstitial cells, enteric neurons, and smooth muscle and thereby affect gastric myoelectrical rhythms,21 shifting electrical activity to bradygastrias (0-2.5cpm) or tachygastrias (3.7- l0.0cpm) as shown in Figure 7.1. All of these influences interact to maintain normal gastric myoelectrical activity during baseline periods and in response to meals or other provocative stimuli. Stimuli that provoke stomach neuromuscular activity range from motion and the illusion of motion to emotionally challenging situations (disgust, anger) to the cephalic phase of digestion (vagal activation in the presence of appetizing food) to the relaxation, contraction, and coordination of stomach neuromuscular responses during and after the ingestion of a wide variety of solid and liquid foodstuffs. Thus, there are many gut-brain and brain-gut interactions to consider when evaluating gastric myoelectrical events during EGG recordings at baseline and after provocative stimuli.

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.

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