scholarly journals Accelerated intestinal transit in inbred mice with an increased number of interstitial cells of Cajal

2005 ◽  
Vol 288 (1) ◽  
pp. G151-G158 ◽  
Author(s):  
Sylvain Bellier ◽  
Nelly R. Da Silva ◽  
Geneviève Aubin-Houzelstein ◽  
Colette Elbaz ◽  
Jean-Marie Vanderwinden ◽  
...  
Keyword(s):  
Small Intestine ◽  
Slow Wave ◽  
Intestinal Motility ◽  
Interstitial Cells Of Cajal ◽  
Inbred Mice ◽  
Inbred Mouse Strain ◽  
Interstitial Cells ◽  
Intestinal Transit ◽  
Wave Frequency ◽  
Cells Of Cajal

The interstitial cells of Cajal (ICC) play an important role in coordinating intestinal motility, and structural alterations in ICC are found in several human digestive diseases. Mouse models with defects in ICC allow a better understanding of their functions. We investigated the pattern of intestinal motility and the distribution of ICC in the PRM/Alf inbred mouse strain, characterized by a selective intestinal lengthening. In PRM/Alf mice, the digestive transit time, evaluated by using thermophilic Bacillus subtilis spores, was normal, indicating accelerated transit. The contractility and slow-wave frequency, recorded on isolated segments from the proximal small intestine, were significantly increased. The number of ICC was also significantly higher along the small intestine and the colon. The concomitant increase of the contractility, the slow-wave frequency, and the number of ICC is consistent with the proposal of a role of ICC number increase in the higher intestinal transit speed. The PRM/Alf model should be useful to further investigate the roles of ICC in the control of digestive motility.

scholarly journals Conditional genetic deletion of Ano1 in interstitial cells of Cajal impairs Ca2+ transients and slow waves in adult mouse small intestine

2017 ◽  
Vol 312 (3) ◽  
pp. G228-G245 ◽  
Author(s):  
John Malysz ◽  
Simon J. Gibbons ◽  
Siva A. Saravanaperumal ◽  
Peng Du ◽  
Seth T. Eisenman ◽  
...  
Keyword(s):  
Small Intestine ◽  
Slow Wave ◽  
Interstitial Cells Of Cajal ◽  
Adult Mouse ◽  
Rank Order ◽  
Interstitial Cells ◽  
Slow Waves ◽  
Functional Reserve ◽  
Mouse Small Intestine ◽  
Cells Of Cajal

Myenteric plexus interstitial cells of Cajal (ICC-MY) in the small intestine are Kit+ electrical pacemakers that express the Ano1/TMEM16A Ca2+-activated Cl– channel, whose functions in the gastrointestinal tract remain incompletely understood. In this study, an inducible Cre-LoxP-based approach was used to advance the understanding of Ano1 in ICC-MY of adult mouse small intestine. KitCreERT2/+;Ano1Fl/Fl mice were treated with tamoxifen or vehicle, and small intestines (mucosa free) were examined. Quantitative RT-PCR demonstrated ~50% reduction in Ano1 mRNA in intestines of conditional knockouts (cKOs) compared with vehicle-treated controls. Whole mount immunohistochemistry showed a mosaic/patchy pattern loss of Ano1 protein in ICC networks. Ca2+ transients in ICC-MY network of cKOs displayed reduced duration compared with highly synchronized controls and showed synchronized and desynchronized profiles. When matched, the rank order for Ano1 expression in Ca2+ signal imaged fields of view was as follows: vehicle controls>>>cKO(synchronized)>cKO(desynchronized). Maintenance of Ca2+ transients’ synchronicity despite high loss of Ano1 indicates a large functional reserve of Ano1 in the ICC-MY network. Slow waves in cKOs displayed reduced duration and increased inter-slow-wave interval and occurred in regular- and irregular-amplitude oscillating patterns. The latter activity suggested ongoing interaction by independent interacting oscillators. Lack of slow waves and depolarization, previously reported for neonatal constitutive knockouts, were also seen. In summary, Ano1 in adults regulates gastrointestinal function by determining Ca2+ transients and electrical activity depending on the level of Ano1 expression. Partial Ano1 loss results in Ca2+ transients and slow waves displaying reduced duration, while complete and widespread absence of Ano1 in ICC-MY causes lack of slow wave and desynchronized Ca2+ transients. NEW & NOTEWORTHY The Ca2+-activated Cl− channel, Ano1, in interstitial cells of Cajal (ICC) is necessary for normal gastrointestinal motility. We knocked out Ano1 to varying degrees in ICC of adult mice. Partial knockout of Ano1 shortened the widths of electrical slow waves and Ca2+ transients in myenteric ICC but Ca2+ transient synchronicity was preserved. Near-complete knockout was necessary for transient desynchronization and loss of slow waves, indicating a large functional reserve of Ano1 in ICC. View this article's corresponding video summary at https://youtu.be/cyPtDP0KLY4 .

scholarly journals Expression of the Regulated Isoform of the Electrogenic Na+/HCO3- Cotransporter, NBCe1, is Enriched in Pacemaker Interstitial Cells of Cajal

2020 ◽  
Author(s):  
Maria-Gabriela Colmenares Aguilar ◽  
Amelia Mazzone ◽  
Seth T Eisenman ◽  
Peter R Strege ◽  
Cheryl E Bernard ◽  
...  
Keyword(s):  
Small Intestine ◽  
Slow Wave ◽  
Interstitial Cells Of Cajal ◽  
Interstitial Cells ◽  
Transcriptional Analysis ◽  
Pacemaker Activity ◽  
Ip3 Receptor ◽  
Gene Transcripts ◽  
Tunica Muscularis ◽  
Cells Of Cajal

Interstitial cells of Cajal (ICC) generate electrical slow waves, which are required for normal gastrointestinal motility. The mechanisms for generation of normal pacemaking are not fully understood. Normal gastrointestinal contractility and electrical slow wave activity depend on the presence of extracellular HCO3-. Previous transcriptional analysis identified enrichment of mRNA encoding the electrogenic Na+/HCO3- cotransporter (NBCe1) gene (Slc4a4) in pacemaker myenteric ICC in mouse small intestine. We aimed to determine the distribution of NBCe1 protein in ICC of the mouse gastrointestinal tract, and to identify the transcripts of the Slc4a4 gene in mouse and human small intestinal tunica muscularis. We determined the distribution of NBCe1-immunoreactivity (NBCe1-IR) by immunofluorescent labeling in mouse and human tissues. In mice, NBCe1-IR was restricted to Kit-positive myenteric ICC of the stomach and small intestine and sub-muscular ICC of the large intestine; that is the slow wave generating subset of ICC. Other sub-types of ICC were NBCe1-negative. Quantitative real time PCR identified >500 fold enrichment of Slc4a4‑207 and Slc4a4‑208 transcripts (IP3-receptor binding protein released by IP3" (IRBIT) regulated isoforms) in Kit expressing cells isolated from KitcreERT2/+, Rpl22tm1.1Psam/Sj mice and from single GFP-positive ICC from Kittm1Rosay mice. Human jejunal tunica muscularis ICC were also NBCe1-positive and SLC4A4‑201 and SLC4A4‑204 RNAs were >300 fold enriched relative to SLC4A4‑202. In summary, NBCe1 protein expressed in ICC with electrical pacemaker function is encoded by Slc4a4 gene transcripts that generate IRBIT regulated isoforms of NBCe1. In conclusion Na+/HCO3- cotransport through NBCe1 contributes to the generation of pacemaker activity in subsets of ICC.

scholarly journals Slow wave propagation and plasticity of interstitial cells of Cajal in the small intestine of diabetic rats

2011 ◽  
Vol 96 (10) ◽  
pp. 1039-1048 ◽  
Author(s):  
Wim J. E. P. Lammers ◽  
H. M. Al-Bloushi ◽  
S. A. Al-Eisaei ◽  
F. A. Al-Dhaheri ◽  
B. Stephen ◽  
...  
Keyword(s):  
Wave Propagation ◽  
Small Intestine ◽  
Slow Wave ◽  
Interstitial Cells Of Cajal ◽  
Interstitial Cells ◽  
Diabetic Rats ◽  
Cells Of Cajal

Sodium current in human intestinal interstitial cells of Cajal

2003 ◽  
Vol 285 (6) ◽  
pp. G1111-G1121 ◽  
Author(s):  
Peter R. Strege ◽  
Yijun Ou ◽  
Lei Sha ◽  
Adam Rich ◽  
Simon J. Gibbons ◽  
...  
Keyword(s):  
Single Cell ◽  
Slow Wave ◽  
Interstitial Cells Of Cajal ◽  
Sodium Current ◽  
Interstitial Cells ◽  
Wave Frequency ◽  
Rt Pcr ◽  
Α Subunit ◽  
Channel Current ◽  
Cells Of Cajal

Interstitial cells of Cajal (ICC) generate the electrical slow wave required for normal gastrointestinal motility. The ionic conductances expressed in human intestinal ICC are unknown. The aim of this study was to determine expression of a Na+ current in human intestinal ICC and to determine the effects of the Na+ current on the slow wave. Visually identified, freshly dissociated, single ICC were verified by the presence of c- kit mRNA by using single-cell RT-PCR. Standard whole cell currents were recorded from patch-clamped ICC held at -100 mV between pulse protocols. A Na+ current was identified in human intestinal ICC. The current activated at -55 mV and peaked at -30 mV. Extracellular N-methyl-d-glucamine abolished and QX-314 (500 μM) blocked the Na+ current, but nifedipine and Ni2+ did not. The Na+ current was activated by shear stress. Single-cell RT-PCR detected mRNA for the Na+ α-subunit SCN5A in single human intestinal ICC. Lidocaine (200 μm) and QX-314 (500 μM) decreased slow wave frequency, and stretch increased slow wave frequency. A mechanosensitive Na+ channel current is present in human intestinal ICC and appears to play a role in the control of intestinal motor function.

scholarly journals Effects of ATP on Pacemaker Activity of Interstitial Cells of Cajal from the Mouse Small Intestine

2018 ◽  
Vol 54 (1) ◽  
pp. 63
Author(s):  
Il Koo Park ◽  
Jin Ho Kim ◽  
Chan Guk Park ◽  
Man Yoo Kim ◽  
Shankar Prasad Parajuli ◽  
...  
Keyword(s):  
Small Intestine ◽  
Interstitial Cells Of Cajal ◽  
Interstitial Cells ◽  
Pacemaker Activity ◽  
Mouse Small Intestine ◽  
Cells Of Cajal

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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