scholarly journals Extracellular Cl−regulates electrical slow waves and setting of smooth muscle membrane potential by interstitial cells of Cajal in mouse jejunum

2017 ◽  
Vol 103 (1) ◽  
pp. 40-57 ◽  
Author(s):  
Siva Arumugam Saravanaperumal ◽  
Simon J. Gibbons ◽  
John Malysz ◽  
Lei Sha ◽  
David R. Linden ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Membrane Potential ◽  
Interstitial Cells Of Cajal ◽  
Interstitial Cells ◽  
Slow Waves ◽  
Muscle Membrane ◽  
Smooth Muscle Membrane ◽  
Cells Of Cajal

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.

Role of gap junctions in structural arrangements of interstitial cells of Cajal and canine ileal smooth muscle

1998 ◽  
Vol 274 (6) ◽  
pp. G1125-G1141 ◽  
Author(s):  
Edwin E. Daniel ◽  
Yu-Fang Wang ◽  
Francisco S. Cayabyab
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Gap Junctions ◽  
Interstitial Cells Of Cajal ◽  
Circular Muscle ◽  
Muscle Cells ◽  
Interstitial Cells ◽  
Slow Waves ◽  
Circular Smooth Muscle ◽  
Cells Of Cajal

We examined the structural and functional basis for pacemaking by interstitial cells of Cajal (ICC) in circular smooth muscle of the canine ileum. Gap junctions were found between ICC of myenteric plexus (MyP), occasionally between MyP ICC and outer circular smooth muscle cells, between individual outer circular smooth muscle cells, between them and ICC of the deep muscular plexus (DMP), and between DMP ICC. No visible gap junctions connected MyP ICC to longitudinal muscle cells or inner circular muscle cells. Occasionally contacts occurred between the two muscle layers. No special structures were found to connect MyP and DMP ICC networks. Octanol concentration dependently reduced the amplitude and frequency of, but did not abolish, slow waves in circular muscle in isolated ileum recorded near the MyP or the DMP. Slow waves triggered from MyP ICC by a current pulse also persisted. Contractile activity was abolished, cells were depolarized, and fast inhibitory junction potentials were reduced by octanol. We conclude that ICC pacemakers of the MyP and DMP utilize gap junctional conductances for pacemaking function but may not require them. Coupling between the two ICC networks may utilize the circular muscle syncytium.

scholarly journals Furthering the debate on the role of interstitial cells of Cajal in enteric inhibitory neuromuscular neurotransmission

2016 ◽  
Vol 311 (3) ◽  
pp. C479-C481 ◽  
Author(s):  
Arun Chaudhury
Keyword(s):  
Interstitial Cells Of Cajal ◽  
Chemical Space ◽  
Critical Role ◽  
Interstitial Cells ◽  
Muscle Membrane ◽  
Smooth Muscle Membrane ◽  
Hyperpolarizing Response ◽  
Braking Process ◽  
Cells Of Cajal

The gut, a muscular organ, performs a critical role in transporting ingested contents, yet it is also controlled to periodically stop transport to maximize digestion and toxin detection. The complex intraluminal composition and rheology challenge the mechanistic requirements of inhibitory neuromuscular neurotransmission. The interstitial cells of Cajal (ICCs)-generated slow wave may tune the promiscuous luminal chemical environment, which prepares the smooth muscle membrane potential for a depolarizing or hyperpolarizing response as needed. Slow waves are abolished during stimulation-induced inhibitory junction potentials (IJPs) due to purinergic-nitrergic tandem neurotransmission. Recent data demonstrating intact IJPs in a genomic knockout of ICCs provide rigorous evidence of the noncontribution of ICCs during evoked neurotransmission. This perspective article discusses the priority areas of investigations in enteric musculomotor transmission, for understanding its near-perfect design for chemical space sensing, as well as diseases in which the luminal transport braking process becomes dysfunctional, leading to delayed gastric emptying or intestinal transit.

Ether-a-go-go-related gene 3 is the main candidate for the E-4031-sensitive potassium current in the pacemaker interstitial cells of Cajal

2008 ◽  
Vol 295 (4) ◽  
pp. G691-G699 ◽  
Author(s):  
Elizabeth J. White ◽  
Sung Jin Park ◽  
Jane A. Foster ◽  
Jan D. Huizinga
Keyword(s):  
Smooth Muscle ◽  
In Situ Hybridization ◽  
Membrane Potential ◽  
Smooth Muscle Cells ◽  
Interstitial Cells Of Cajal ◽  
Muscle Cells ◽  
Interstitial Cells ◽  
Related Gene ◽  
Cells Of Cajal

The interstitial cells of Cajal (ICC), as pacemaker cells of the gut, contribute to rhythmic peristalsis and muscle excitability through initiation of slow-wave activity, which subsequently actively propagates into the musculature. An E-4031-sensitive K+ current makes a critical contribution to membrane potential in ICC. This study provides novel features of this current in ICC in physiological solutions and seeks to identify the channel isoform. In situ hybridization and Kit immunohistochemistry were combined to assess ether-a-go-go-related gene (ERG) mRNA expression in ICC in mouse jejunum, while the translated message was assessed by immunofluorescence colocalization of ERG and Kit proteins. E-4031-sensitive currents in cultured ICC were studied by the whole cell patch-clamp method, with physiological K+ concentration in the bath and the pipette. In situ hybridization combined with Kit immunohistochemistry detected m-erg1 and m-erg3, but not m-erg2, mRNA in ICC. ERG3 protein was colocalized with Kit-immunoreactive ICC in jejunum sections, but ERG1 protein was visualized only in the smooth muscle cells. At physiological K+ concentration, the E-4031-sensitive outward current in ICC was different from its counterpart in cardiac and gut smooth muscle cells. In particular, inactivation upon depolarization and recovery from inactivation by hyperpolarization were modest in ICC. In summary, the E-4031-sensitive currents influence the kinetics of the pacemaker activity in ICC and contribute to maintenance of the resting membrane potential in smooth muscle cells, which together constitute a marked effect on tissue excitability. Whereas this current is mediated by ERG1 in smooth muscle, it is primarily mediated by ERG3 in ICC.

Slow-wave activity in colon: role of network of submucosal interstitial cells of Cajal

1991 ◽  
Vol 260 (4) ◽  
pp. G636-G645 ◽  
Author(s):  
R. Serio ◽  
C. Barajas-Lopez ◽  
E. E. Daniel ◽  
I. Berezin ◽  
J. D. Huizinga
Keyword(s):  
Smooth Muscle ◽  
Slow Wave ◽  
Interstitial Cells Of Cajal ◽  
Circular Muscle ◽  
Interstitial Cells ◽  
Wave Activity ◽  
Slow Waves ◽  
Slow Wave Activity ◽  
Plateau Potentials ◽  
Cells Of Cajal

The present study compares the electrophysiological properties of two preparations dissected from the canine colon circular muscle layer: first, containing the submucosal network of interstitial cells of Cajal (ICC) with two to four associated smooth muscle cell layers, and second, a circular muscle preparation devoid of the submucosal ICC network. In the ICC-rich preparations, consistent slow-wave activity was observed with prolonged plateau potentials of approximately 10-s duration. The plateau potentials were sensitive to D 600. In approximately 45% of circular muscle preparations devoid of the submucosal ICC network (confirmed using electron microscopy) slow waves, of different waveshape, were recorded at frequencies identical to those in whole circular muscle preparations. These slow waves did not show a plateau potential. Compared with ICC-rich preparations with a resting membrane potential of about -80 mV, circular muscle preparations had lower membrane potentials, about -70 mV when active, and about -60 mV when quiescent. Heptanol (1 mM) electrically uncoupled cells, since it abolished electrotonic current spread and allowed measurement of the input resistance by intracellular current injection. Heptanol also affected ionic conductances. Heptanol abolished slow waves; the underlying mechanism needs further investigation. In the presence of heptanol, cells in the isolated ICC network and in circular smooth muscle preparations showed spontaneous hyperpolarizing potential fluctuations at a frequency of four to six per second. These oscillations were abolished by current-induced hyperpolarization and TEA (30 mM) and are therefore likely due to spontaneously active K+ conductance.

Pathways of slow-wave propagation in proximal colon of cats

1990 ◽  
Vol 258 (6) ◽  
pp. G894-G903 ◽  
Author(s):  
J. L. Conklin ◽  
C. Du
Keyword(s):  
Wave Propagation ◽  
Smooth Muscle ◽  
Slow Wave ◽  
Interstitial Cells Of Cajal ◽  
Muscularis Propria ◽  
Interstitial Cells ◽  
Proximal Colon ◽  
Slow Waves ◽  
Cells Of Cajal ◽  
Circular Axis

Colonic slow waves (SWs) are generated by nonneuronal cells located at the interface of the submucosa and muscularis propria. It has been proposed that SWs arise from a complex of nerves, interstitial cells of Cajal, and smooth muscle found at this location. These experiments test the hypothesis that the propagation of colonic SWs depends on an intact interface between the submucosa and muscularis propria. The electromyogram was recorded from segments of the proximal colon of the cat. All intact tissues generated SWs that propagated in the long and circumferential axes of the colon. Tetrodotoxin did not disrupt SW propagation in either axis. Transection of tissues between recording sites interrupted the spread of SWs in both axes. Transection of the submucosa disrupted the longitudinal spread of SWs, whereas transection of the muscularis propria did not. Removing the submucosa from the midportion of tissue segments oriented in the long axis of the colon resulted in a loss of SWs from the segment devoid of submucosa. Transection of the submucosa of tissue segments oriented in the circular axis of the colon did not disrupt circumferential propagation of SWs. Dissecting a 1-cm-wide segment of submucosa from the midportion of such a circularly oriented tissue did not disrupt the circumferential spread of SWs, and SWs were recorded from the muscle segment that was devoid of submucosa. SWs were not recorded from the segment devoid of submucosa when it was isolated from adjacent intact segments. The data support the hypothesis that the regeneration of SWs during their longitudinal propagation takes place at the interface between the submucosa and muscularis propria.

Canine colonic circular muscle generates action potentials without the pacemaker component

1994 ◽  
Vol 72 (1) ◽  
pp. 70-81 ◽  
Author(s):  
Louis W. C. Liu ◽  
Jan D. Huizinga
Keyword(s):  
Smooth Muscle ◽  
Calcium Channel ◽  
Action Potentials ◽  
Interstitial Cells Of Cajal ◽  
Longitudinal Muscle ◽  
Circular Muscle ◽  
Muscle Cells ◽  
Interstitial Cells ◽  
Slow Waves ◽  
Cells Of Cajal

Two dominant types of action potentials in canine colon are slow wave type action potentials (slow waves) and spike-like action potentials (SLAPs). The slow waves, originating at the submuscular surface where a network of interstitial cells of Cajal (ICCs) is found, possess a pacemaker component. Activation of the pacemaker component is insensitive to voltage changes and L-type calcium channel blockers, and is postulated to involve a metabolic clock sensitive to cyclic AMP. SLAPs are more prominent in the longitudinal muscle. To understand the contribution circular muscle cells make to the generation of these action potentials, a circular muscle preparation (devoid of the submuscular ICC – smooth muscle network, longitudinal muscle, and myenteric plexus) was developed. Circular muscle preparations were spontaneously quiescent, with a resting membrane potential of −62.9 ± 0.6 mV. Ba2+ (0.5 mM) depolarized the cells to −51.8 ± 0.6 mV and induced electrical oscillations with a frequency, duration, amplitude, and rate of rise equal to 6.6 ± 0.4 cpm, 2.2 ± 0.2 s, 19.4 ± 0.9 mV, and 21.8 ± 1.7 mV/s, respectively. In most cases, Ba2+-induced oscillations were preceded by a prepotential of 4.4 ± 0.3 mV, with a rate of rise of 1.1 ± 0.1 mV/s. Ba2+-induced oscillations were abolished by 1 μM D600 as well as by repolarization of 6–12 mV. Addition of 0.1 μM Bay K8644 in the presence of Ba2+ further depolarized circular muscle cells to −42.4 ± 0.8 mV and increased the oscillation frequency to 16.8 ± 1.8 cpm. The electrical oscillations induced in circular muscle preparations by Ba2+ and Bay K8644 were similar to the SLAPs exhibited by the isolated longitudinal muscle layer, indicating that generation of SLAPs is an intrinsic property of smooth muscle cells. Forskolin (1 μM), previously shown to dramatically decrease the frequency but not the amplitude of slow waves in preparations including the submuscular ICC network, decreased the amplitude of the Ba2+-induced oscillations in circular muscle preparations without changing the frequency. These results provide strong evidence for the hypothesis that the submuscular ICC – smooth muscle network is essential for the initiation of the pacemaker component of the colonic slow waves. The mechanism for regulating the frequency of slow waves is different from that responsible for the Ba2+-induced oscillations in circular muscle preparations. Circular muscle cells are shown to be excitable and capable of generating oscillatory activity dominated by L-type calcium channel activity, which is regulated by K+ conductance.Key words: interstitial cells of Cajal, smooth muscle, dog colon, barium chloride, potassium conductance, Bay K8644, pacemaking activity.

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.

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