Do gap junctions play a role in nerve transmissions as well as pacing in mouse intestine?

2007 ◽  
Vol 292 (3) ◽  
pp. G734-G745 ◽  
Author(s):  
E. E. Daniel ◽  
Ahmed El Yazbi ◽  
Marco Mannarino ◽  
Gary Galante ◽  
Geoffrey Boddy ◽  
...  
Keyword(s):  
Gap Junctions ◽  
Gap Junction ◽  
Interstitial Cells Of Cajal ◽  
Circular Muscle ◽  
Electrical Field Stimulation ◽  
Cell Types ◽  
Interstitial Cells ◽  
Glycyrrhetinic Acid ◽  
Mouse Intestine ◽  
Cells Of Cajal

Varicosities of nitrergic and other nerves end on deep muscular plexus interstitial cells of Cajal or on CD34-positive, c- kit-negative fibroblast-like cells. Both cell types connect to outer circular muscle by gap junctions, which may transmit nerve messages to muscle. We tested the hypotheses that gap junctions transmit pacing messages from interstitial cells of Cajal of the myenteric plexus. Effects of inhibitors of gap junction conductance were studied on paced contractions and nerve transmissions in small segments of circular muscle of mouse intestine. Using electrical field stimulation parameters (50 V/cm, 5 pps, and 0.5 ms) which evoke near maximal responses to nitrergic, cholinergic, and apamin-sensitive nerve stimulation, we isolated inhibitory responses to nitrergic nerves, inhibitory responses to apamin-sensitive nerves and excitatory responses to cholinergic nerves. 18β-Glycyrrhetinic acid (10, 30, and 100 μM), octanol (0.1, 0.3, and 1 mM) and gap peptides (300 μM of40Gap27,43Gap26,37,43Gap27) all failed to abolish neurotransmission. 18β-Glycyrrhetinic acid inhibited frequencies of paced contractions, likely owing to inhibition of l-type Ca2+channels in smooth muscle, but octanol or gap peptides did not. 18β-Glycyrrhetinic acid and octanol, but not gap peptides, reduced the amplitudes of spontaneous and nerve-induced contractions. These reductions paralleled reductions in contractions to exogenous carbachol. Additional experiments with gap peptides in both longitudinal and circular muscle segments after NG-nitro-l-arginine and TTX revealed no effects on pacing frequencies. We conclude that gap junction coupling may not be necessary for pacing or nerve transmission to the circular muscle of the mouse intestine.

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.

Proteins of interstitial cells of Cajal and intestinal smooth muscle, colocalized with caveolin-1

2005 ◽  
Vol 288 (3) ◽  
pp. G571-G585 ◽  
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.

Structural effects of exposure of smooth muscle in sucrose gap apparatus

1987 ◽  
Vol 252 (1) ◽  
pp. C77-C87 ◽  
Author(s):  
E. E. Daniel ◽  
V. Posey-Daniel ◽  
L. P. Jager ◽  
I. Berezin ◽  
J. Jury
Keyword(s):  
Smooth Muscle ◽  
Gap Junctions ◽  
Interstitial Cells Of Cajal ◽  
Structural Changes ◽  
Circular Muscle ◽  
Interstitial Cells ◽  
Structural Effects ◽  
Smooth Muscle Tissue ◽  
Sucrose Gap ◽  
Cells Of Cajal

Structural changes were studied over time of a smooth muscle tissue (opossum esophagus circular muscle) exposed in various compartments of a functioning single sucrose gap. The tissues in the Krebs-perfused compartment were qualitatively normal, possessing nerve profiles with little damage, normal appearing smooth muscle and interstitial cells of Cajal as well as gap junctions between muscle cells and interstitial cells. However, in the sucrose compartment tissues had serious damage to smooth muscle, interstitial cells and nerves, and normal gap junctions disappeared. There was also damage to all these structures in tissues exposed to KCl, but most striking was the disappearance of most interstitial cells. These studies raise serious questions about the assumptions underlying the basis for functioning of multicellular tissues in the sucrose gap.

scholarly journals Loss of nitric oxide-mediated inhibition of purine neurotransmitter release in the colon in the absence of interstitial cells of Cajal

2017 ◽  
Vol 313 (5) ◽  
pp. G419-G433 ◽  
Author(s):  
Leonie Durnin ◽  
Andrea Lees ◽  
Sheerien Manzoor ◽  
Kent C. Sasse ◽  
Kenton M. Sanders ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Interstitial Cells Of Cajal ◽  
Colonic Motility ◽  
Circular Muscle ◽  
Electrical Field Stimulation ◽  
Interstitial Cells ◽  
Partial Loss ◽  
Purinergic Neurotransmission ◽  
Cells Of Cajal

Regulation of colonic motility depends on the integrity of enteric inhibitory neurotransmission mediated by nitric oxide (NO), purine neurotransmitters, and neuropeptides. Intramuscular interstitial cells of Cajal (ICC-IM) and platelet-derived growth factor receptor-α-positive (PDGFRα+) cells are involved in generating responses to NO and purine neurotransmitters, respectively. Previous studies have suggested a decreased nitrergic and increased purinergic neurotransmission in KitW/KitW-v ( W/Wv) mice that display lesions in ICC-IM along the gastrointestinal tract. However, contributions of NO to these phenotypes have not been evaluated. We used small-chamber superfusion assays and HPLC to measure the spontaneous and electrical field stimulation (EFS)-evoked release of nicotinamide adenine dinucleotide (NAD+)/ADP-ribose, uridine adenosine tetraphosphate (Up4A), adenosine 5′-triphosphate (ATP), and metabolites from the tunica muscularis of human, monkey, and murine colons and circular muscle of monkey colon, and we tested drugs that modulate NO levels or blocked NO receptors. NO inhibited EFS-evoked release of purines in the colon via presynaptic neuromodulation. Colons from W/Wv, Nos1−/−, and Prkg1−/− mice displayed augmented neural release of purines that was likely due to altered nitrergic neuromodulation. Colons from W/Wv mice demonstrated decreased nitrergic and increased purinergic relaxations in response to nerve stimulation. W/Wv mouse colons demonstrated reduced Nos1 expression and reduced NO release. Our results suggest that enhanced purinergic neurotransmission may compensate for the loss of nitrergic neurotransmission in muscles with partial loss of ICC. The interactions between nitrergic and purinergic neurotransmission in the colon provide novel insight into the role of neurotransmitters and effector cells in the neural regulation of gastrointestinal motility. NEW & NOTEWORTHY This is the first study investigating the role of nitric oxide (NO) and intramuscular interstitial cells of Cajal (ICC-IM) in modulating neural release of purines in colon. We found that NO inhibited release of purines in human, monkey, and murine colons and that colons from KitW/KitW-v ( W/Wv) mice, which present with partial loss of ICC-IM, demonstrated augmented neural release of purines. Interactions between nitrergic and purinergic neurotransmission may affect motility in disease conditions with ICC-IM deficiencies.

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.

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.

scholarly journals Roles of interstitial cells of Cajal in regulation of motility of the mouse intestine.

2004 ◽  
Vol 123 (3) ◽  
pp. 170-178 ◽  
Author(s):  
Akikazu FUJITA ◽  
Yutaka OKISHIO ◽  
Tadayoshi TAKEUCHI ◽  
Fumiaki HATA
Keyword(s):  
Interstitial Cells Of Cajal ◽  
Interstitial Cells ◽  
Mouse Intestine ◽  
Cells Of Cajal

Pacemaker potentials generated by interstitial cells of Cajal in the murine intestine

2005 ◽  
Vol 288 (3) ◽  
pp. C710-C720 ◽  
Author(s):  
Yoshihiko Kito ◽  
Sean M. Ward ◽  
Kenton M. Sanders
Keyword(s):  
Interstitial Cells Of Cajal ◽  
Circular Muscle ◽  
Muscle Cells ◽  
Interstitial Cells ◽  
Slow Waves ◽  
Pacemaker Activity ◽  
Dependent Manner ◽  
Plateau Potential ◽  
Pacemaker Potentials ◽  
Cells Of Cajal

Pacemaker potentials were recorded in situ from myenteric interstitial cells of Cajal (ICC-MY) in the murine small intestine. The nature of the two components of pacemaker potentials (upstroke and plateau) were investigated and compared with slow waves recorded from circular muscle cells. Pacemaker potentials and slow waves were not blocked by nifedipine (3 μM). In the presence of nifedipine, mibefradil, a voltage-dependent Ca2+ channel blocker, reduced the amplitude, frequency, and rate of rise of upstroke depolarization (d V/d tmax) of pacemaker potentials and slow waves in a dose-dependent manner (1–30 μM). Mibefradil (30 μM) changed the pattern of pacemaker potentials from rapidly rising, high-frequency events to slowly depolarizing, low-frequency events with considerable membrane noise (unitary potentials) between pacemaker potentials. Caffeine (3 mM) abolished pacemaker potentials in the presence of mibefradil. Pinacidil (10 μM), an ATP-sensitive K+ channel opener, hyperpolarized ICC-MY and increased the amplitude and d V/d tmax without affecting frequency. Pinacidil hyperpolarized smooth muscle cells and attenuated the amplitude and d V/d tmax of slow waves without affecting frequency. The effects of pinacidil were blocked by glibenclamide (10 μM). These data suggest that slow waves are electrotonic potentials driven by pacemaker potentials. The upstroke component of pacemaker potentials is due to activation of dihydropyridine-resistant Ca2+ channels, and this depolarization entrains pacemaker activity to create the plateau potential. The plateau potential may be due to summation of unitary potentials generated by individual or small groups of pacemaker units in ICC-MY. Entrainment of unitary potentials appears to depend on Ca2+ entry during upstroke depolarization.

scholarly journals Effects of gap junction inhibition on contraction waves in the murine small intestine in relation to coupled oscillator theory

2015 ◽  
Vol 308 (4) ◽  
pp. G287-G297 ◽  
Author(s):  
Sean P. Parsons ◽  
Jan D. Huizinga
Keyword(s):  
Small Intestine ◽  
Gap Junction ◽  
Interstitial Cells Of Cajal ◽  
Interstitial Cells ◽  
Coupled Oscillator ◽  
Motor Patterns ◽  
Mapping System ◽  
Murine Small Intestine ◽  
Cells Of Cajal ◽  
Oscillator Theory

Waves of contraction in the small intestine correlate with slow waves generated by the myenteric network of interstitial cells of Cajal. Coupled oscillator theory has been used to explain steplike gradients in the frequency (frequency plateaux) of contraction waves along the length of the small intestine. Inhibition of gap junction coupling between oscillators should lead to predictable effects on these plateaux and the wave dislocation (wave drop) phenomena associated with their boundaries. It is these predictions that we wished to test. We used a novel multicamera diameter-mapping system to measure contraction along 25- to 30-cm lengths of murine small intestine. There were typically two to three plateaux per length of intestine. Dislocations could be limited to the wavefronts immediately about the terminated wave, giving the appearance of a three-pronged fork, i.e., a fork dislocation; additionally, localized decreases in velocity developed across a number of wavefronts, ending with the terminated wave, which could appear as a fork, i.e., slip dislocations. The gap junction inhibitor carbenoxolone increased the number of plateaux and dislocations and decreased contraction wave velocity. In some cases, the usual frequency gradient was reversed, with a plateau at a higher frequency than its proximal neighbor; thus fork dislocations were inverted, and the direction of propagation was reversed. Heptanol had no effect on the frequency or velocity of contractions but did reduce their amplitude. To understand intestinal motor patterns, the pacemaker network of the interstitial cells of Cajal is best evaluated as a system of coupled oscillators.

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