Cholinergic and nitrergic innervation of ICC-DMP and ICC-IM in the human small intestine (original) (raw)
Related papers
The Journal of physiology, 2004
Recent studies have demonstrated that intramuscular interstitial cells of Cajal (ICC) are preferential targets for neurotransmission in the stomach. Terminals of enteric motor neurones also form tight, synaptic-like contacts with ICC in the small intestine and colon, but little is known about the role of these cells in neurotransmission. ICC at the deep muscular plexus (ICC-DMP) of the small intestine express neurokinin 1 receptors (NK1R) and internalize these receptors in response to exogenous substance P. We used NK1R internalization as an assay of functional innervation of ICC-DMP in the murine small intestine. Under basal conditions NK1R-like immunoreactivity (NK1R-LI) was mainly observed in ICC-DMP (519 cells counted, 100% were positive) and myenteric neurones. ICC-DMP were closely apposed to substance P-containing nerve fibres. Of 338 ICC-DMP examined, 65% were closely associated with at least one substance P-positive nerve fibre, 32% were associated with at least two, 2% were...
The Journal of Physiology, 2006
Interstitial cells of Cajal (ICC) provide important regulatory functions in the motor activity of the gastrointestinal tract. In the small intestine, ICC in the myenteric region (ICC-MY), between the circular and longitudinal muscle layers, generate and propagate electrical slow waves. Another population of ICC lies in the plane of the deep muscular plexus (ICC-DMP), and these cells are closely associated with varicose nerve terminals of enteric motor neurons. Here we tested the hypothesis that ICC-DMP mediate excitatory and inhibitory neural inputs in the small bowel. ICC-DMP develop largely after birth. ICC-DMP, with receptor tyrosine kinase Kit-like immunoreactivity, appear first in the jejunum and then in the ileum. We performed electrophysiological experiments on mice immediately after birth (P0) or at 10 days post partum (P10) to determine whether neural responses follow development of ICC-DMP. At P0, slow-wave activity was present in the jejunum, but neural responses were poorly developed. By P10, after ICC-DMP developed, both cholinergic excitatory and nitrergic inhibitory neural responses were intact. Muscles of P0 mice were also put into organotypic cultures and treated with a neutralizing Kit antibody. Neural responses developed in culture within 3-6 days in control muscles, but blocking Kit caused loss of ICC and loss of cholinergic and nitrergic neural responses. Non-cholinergic excitatory responses remained after loss of ICC-DMP. Our observations are consistent with the idea that cholinergic and nitrergic motor neural inputs are mediated, to a large extent, via ICC-DMP. Thus, ICC-DMP appear to serve a function in the small intestine that is similar to the role of the intramuscular ICC in the stomach.
Inhibitory innervation of colonic smooth muscle cells and interstitial cells of Cajal
Canadian Journal of Physiology and Pharmacology, 1990
The effect of neural inhibition on the electrical activities of circular and longitudinal colonic smooth muscle was investigated. In addition, a comparative study was carried out between circular muscle preparations with and without the "submucosal" and "myenteric plexus" network of interstitial cells of Cajal (ICC) to study innervation of the "submucosal" ICC and to investigate whether or not the ICC network is an essential intermediary system for inhibitory innervation of smooth muscle cells. Electrical stimulation of intrinsic nerves in the presence of atropine caused inhibitory junction potentials (ijps) throughout the circular and longitudinal muscle layers. The ijp amplitude depended on the membrane potential and not on the location of the muscle cells with respect to the ICC network. Neurally mediated inhibition of the colon resulted in a reduction in amplitude and duration of slow wave type action potentials in circular and abolishment of spike-...
Interstitial cells of Cajal mediate cholinergic neurotransmission from enteric motor neurons
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2000
Interstitial cells of Cajal (ICC) are interposed between enteric neurons and smooth muscle cells in gastrointestinal muscles. The role of intramuscular ICC (IC-IM) in mediating enteric excitatory neural inputs was studied using gastric fundus muscles of wild-type animals and W/W(v) mutant mice, which lack IC-IM. Excitatory motor neurons, labeled with antibodies to vesicular acetylcholine transporter or substance-P, were closely associated with IC-IM. Immunocytochemistry showed close contacts between enteric neurons and IC-IM. IC-IM also formed gap junctions with smooth muscle cells. Electrical field stimulation yielded fast excitatory junction potentials in the smooth muscle that were blocked by atropine. Neural responses were greatly reduced in muscles of W/W(v) animals. Loss of cholinergic responses in W/W(v) muscles seemed to be caused by the loss of close synaptic contacts between motor neurons and IC-IM, because these muscles were not less responsive to exogenous acetylcholine ...
Mounting evidence against the role of ICC in neurotransmission to smooth muscle in the gut
American Journal of Physiology-Gastrointestinal and Liver Physiology, 2009
How nerves transmit their signals to regulate activity of smooth muscle is of fundamental importance to autonomic and enteric physiology, clinical medicine, and therapeutics. A traditional view of neurotransmission to smooth muscles has been that motor nerve varicosities release neurotransmitters that act on receptors on smooth muscles to cause their contraction or relaxation via electromechanical and pharmacomechanical signaling pathways in the smooth muscle. In recent years, an old hypothesis that certain interstitial cells of Cajal (ICC) may transduce neural signals to smooth muscle cells has been resurrected. This later hypothesis is based on indirect evidence of closer proximity and presence of synapses between the nerve varicosities and ICC, gap junctions between ICC and smooth muscles, and presence of receptors and signaling pathways for the neurotransmitters and ICC. This indirect evidence is at best circumstantial. The direct evidence is based on the reports of loss of neur...
Microscopy Research and Technique, 2009
The relationship between the interstitial cells of Cajal (ICC) and enteric nerves or smooth muscles cells is not fully defined. Presently, distribution and appearance of ICC in the rat stomach and duodenum was studied by immunohistochemistry, electron microscopy, and threedimensional reconstruction. c-kit expressing ICC were regularly observed in the Auerbach's myenteric plexus (AP) of the stomach and duodenum. ICC in stomach and duodenum muscle layers was dissimilarly distributed. c-kit immunoreactive cells were sparsely distributed in the stomach circular muscle layer but were abundant in the duodenum deep muscular plexus (DMP). Electron microscopy revealed that stomach ICC-AP were irregular ovals with few cytoplasmic processes, and possessed an electron-dense cytoplasm, numerous mitochondria, intermediate filaments, and caveolae. Duodenum and stomach ICC-AP were similar in appearance. Ultrastructure observations and three-dimensional reconstructions revealed ICC-AP processes wrapping the nerve fibers and projecting into the space between smooth muscle cells. While ICC-AP was occasionally close to enteric nerves or smooth muscle cells, no connections were observed. ICC-DMP in duodenum was elongated and adopted the same cell axis orientation as the circular muscle cells. Unlike ICC-AP, ICC-DMP formed gap junctions with smooth muscle cells and had close contact with nerves. These results indicate that ICC-AP is regularly distributed in stomach and duodenum, while ICC-DMP is exclusively located in the duodenum. ICC-DMP, which possess gap junctions and closely contacts nerves, may participate in neuromuscular transmission. Microsc. Res. Tech. 72:951-956, 2009. V
Interstitial cells of Cajal and electrical activity of smooth muscle in porcine ileum
Acta Physiologica, 2006
Aim: To identify the interstitial cells of Cajal in the porcine ileum for the first time immunohistochemically and to examine the electrical properties of intestinal smooth muscle in the same region. Methods: In vitro intracellular microelectrode recordings were made from smooth muscle cells in cross-sectional preparations from abattoir-derived healthy porcine ileum. Immunohistochemical labelling of interstitial cells of Cajal was performed using an anti-Kit antibody. Results: Slow waves were recorded in the circular muscle layer of all ileal preparations. The mean resting membrane potential of smooth muscle cells was)61.0 AE 1.3 mV. Slow waves had a mean amplitude of 8.5 AE 0.5 mV, a frequency of 9.9 AE 0.1 cycles per minute and a duration of 5.6 AE 0.1 s. A waxing and waning pattern of slow wave activity was occasionally observed. In addition, higher frequency spiking activity associated with contractions was observed in some recordings. The L-type calcium channel blocker nifedipine abolished both the spiking activity and the contractions, but had no significant effect on slow wave characteristics. Current-injection manipulation of the resting membrane potential had no effect on slow wave amplitude, frequency or duration. Kit-immunoreactive interstitial cells of Cajal were identified in the ileal samples and were present in the region of the myenteric plexus and in the circular and longitudinal muscle layers. Conclusion: This study recorded slow waves in vitro and demonstrated immunohistochemically the presence of interstitial cells of Cajal in the normal porcine ileum. This study forms a basis for future physiological and pathophysiological comparative studies of intestinal motility.
Cell and tissue research, 2003
Morphological studies have shown synaptic-like structures between enteric nerve terminals and interstitial cells of Cajal (ICC) in mouse and guinea pig gastrointestinal tracts. Functional studies of mice lacking certain classes of ICC have also suggested that ICC mediate enteric motor neurotransmission. We have performed morphological experiments to determine the relationship between enteric nerves and ICC in the canine gastric antrum with the hypothesis that conservation of morphological features may indicate similar functional roles for ICC in mice and thicker-walled gastrointestinal organs of larger mammals. Four classes of ICC were identified based on anatomical location within the tunica muscularis. ICC in the myenteric plexus region (IC-MY) formed a network of cells that were interconnected to each other and to smooth muscle cells by gap junctions. Intramuscular interstitial cells (IC-IM) were found in muscle bundles of the circular and longitudinal layers. ICC were located al...