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Interstitial cells of Cajal

Lars Thuneberg

10.1002/cphy.cp060110

Source: Supplement 16: Handbook of Physiology, The Gastrointestinal System, Motility and Circulation

Originally published: 1989

Published online: January 2011

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Some Characteristics of Interstitial Cells of Cajal
2 Small Intestine
2.1 ICC AP, Associated with Auerbach'S Plexus
2.2 ICC SS, Located in Subserous Compartment
2.3 ICC DMP, Associated with deep Muscular Plexus
2.4 ICC CM, Associated with Nerves in Interstices of Main, Outer Layer of Circular Muscle Coat
3 Esophagus and Stomach
3.1 General Organization
3.2 Functions of Esophageal and Gastric ICC
4 Large Intestine
4.1 ICC, Associated with Nerves Of Longitudinal Muscle Coat and with Auerbach'S Plexus
4.2 ICC, Associated with Submuscular Plexus
5 Summary
6 Addendum
Figure 1. Figure 1.

Rat ileocecal junction. Ganglionic collar was suggested to represent a local specialization of Auerbach's plexus, with intermediate cells (ICC AP) interposed between ganglion cells and muscle cells.

From Keith 80
Figure 2. Figure 2.

Rabbit intestine; vital staining with methylene blue. Interstitial cells (ICC AP) associated with Auerbach's plexus.

From Ramón y Cajal 100b)
Figure 3. Figure 3.

Guinea pig small intestine; vital staining with methylene blue. ICC AP plexus partly associated with a nerve fascicle (A) and a ganglion (B) of Auerbach's plexus. Scale, 50 μm.

From Taxi 121
Figure 4. Figure 4.

Cat ileum. ICC (arrows) in circular muscle coat. Number and appearance of cells suggest that they are located between the two subdivisions of circular muscle coat (ICC DMP). Scale, 100 μm.

From Vajda and Fehér 128
Figure 5. Figure 5.

Diagrammatic representation of muscularis externa of mouse small intestine. Three types of ICC are depicted: ICC AP (ICC I) associated with Auerbach's plexus (AP) in interval between the longitudinal muscle coat (LM) and outer lamina of circular muscle (CM‐OL); ICC SS (ICC II), unassociated with neural elements in interval between mesothelium (M) and LM; ICC DMP (ICC III), associated with deep muscular plexus (plexus muscularis profundus, PMP) in interval between outer and inner laminae of circular muscle (CM‐OL, CM‐IL). At all three levels ICC contact and envelop macrophage‐like cells (MLC). As a fourth type of ICC (ICC CM), cells with fibroblast features, which accompany nerve fascicles in interstices of CM‐OL, may be distinguished. ICC CM not shown in diagram.

From Thuneberg 124
Figure 6. Figure 6.

Mouse small intestine; stained with methylene blue. Contrast is high, in spite of specimen thickness (intact intestine), because of selectivity of methylene blue for ICC AP. Few, scattered longitudinal muscle cells are also stained. Absence of stained ICC AP in lower right corner is not due to absence of ICC AP. Outline of Auerbach's plexus is faintly visible because of a condensation of ICC AP plexus, mainly around primary nerve fascicles. Scale, 0.5 mm.
Figure 7. Figure 7.

Mouse small intestine; whole mount stained with methylene blue. ICC AP plexus with complex associations of processes. Cell with broad, flat processes (upper right corner) is embracing a ganglion. C, capillary. Scale, 25 μm.
Figure 8. Figure 8.

Cat small intestine. Area between longitudinal (L) and circular (C) muscle coats. Cells marked II, with oval nuclei (N), and interconnected by desmosome‐like junctions (small arrows), may correspond to ICC AP of mouse small intestine. A, axon; large arrows, basal lamina of muscle cells. Scale, 1 μm.

From Taylor et al. 122
Figure 9. Figure 9.

Mouse small intestine. Section tangential to ICC AP plexus. A: ICC AP (with dark cytoplasm after methylene blue staining) are enveloping an MLC. SM, smooth muscle cells of both layers. B and C: cytoplasmic details of ICC AP processes (area between arrows in A). Note interdigitation of processes, numerous mitochondria, presence of gap junctions between ICC AP (arrows), dominance of thin filaments in narrow processes, intermediate filaments in broader processes, and caveolae with associated smooth cisternae. Scale, 5 μm (A), 0.5 μm (B and C).

From Thuneberg 124
Figure 10. Figure 10.

Mouse small intestine. ICC AP (IC) process with highly developed smooth endoplasmic reticulum, forming subsurface cisternae close to caveolae, similar to arrangement in smooth muscle cells (SM). A basal lamina is present (arrows). Scale, 1 μm.

Micrograph courtesy of H. B. Mikkelsen
Figure 11. Figure 11.

Mouse small intestine. Four vesiculated axonal varicosities (arrows) of small (tertiary) fascicle, in close contact with ICC AP (IC), SM, smooth muscle cells. Scale, 0.5 μm.
Figure 12. Figure 12.

Mouse small intestine. Fluorescence micrographs of MLC after uptake of fluorescein‐labeled dextran. Ramified cells in focus, MLC between the longitudinal and circular muscle layers. Out of focus: subserous MLC, forming longitudinal rows. Note lack of connections between MLC and (in A) association of MLC with faintly visible Auerbach's plexus and with capillaries. Scale, 100 μm (A), 25 μm (B).

From Mikkelsen et al. 95
Figure 13. Figure 13.

Mouse small intestine; isolated musculature stained with methylene blue. Circular muscle layer has been partially separated from longitudinal muscle and bent back along oblique line. ICC AP remain associated with longitudinal muscle layer (lighter triangular area). Scale, 100 μm.

From Thuneberg et al. 126
Figure 14. Figure 14.

Mouse small intestine. Intracellular records of electrical activity, all from same intestinal preparation, which is incubated in a medium with added methylene blue. A: unstained area. B, C, D, and inset: area with selectively stained ICC AP (cf. Fig. 7), at time 10 min (B), 27 min (C), and 33 min (D) after sacrifice of animal. Arrow: He‐Ne laser on. Inset: impalement of another cell after 2‐min illumination. Laser illumination had no effect on slow waves in areas where ICC AP were unstained. Scales, 20 mV and 10 s.

From Thuneberg et al. 125
Figure 15. Figure 15.

Mouse small intestine; methylene blue staining of ICC AP and contraction nodes of smooth muscle cells (longitudinal muscle coat). Note correspondence between positions of ICC AP processes and contraction nodes. Scale, 50 μm.

From Thuneberg 124
Figure 16. Figure 16.

Mouse small intestine. Isolated musculature grown in tissue culture for a few days. Rim of tissue expiant at top right; from this has grown a bundle of parallel, ribbon‐shaped smooth muscle cells (SM, longitudinal axis indicated). N, nucleus of ramified, spontaneously contractile cell (ICC?), contacting several smooth muscle cells and connected by long, contractile process (arrows) to cells of expiant. Scale, 25 μm.
Figure 17. Figure 17.

Direct (left) and indirect (right) neural control of smooth muscle. 1) Axons; 2 and 3) intercalated cells of two types: a fibroblast‐like cell (2) and a macrophage‐like cell (3); 4) smooth muscle cell.

From Feyrter 52
Figure 18. Figure 18.

Mouse duodenum. ICC(AP) extending through entire thickness of longitudinal muscle. CAP, lumen of capillary between muscle layers. SER, serosal surface. ICC contacts two processes with ultrastructural characteristics of ICC SS. Scale, 5 μm.

Micrograph courtesy of J. J. Rumessen
Figure 19. Figure 19.

Guinea pig small intestine; Golgi method. Deep muscular plexus or plexus muscularis profundus (B, right) with associated ICC DMP (A, left). Meshes of plexus, and ICC, are elongated in direction parallel to cells of circular muscle (top to bottom); a, b, f, ICC; c, positions of unstained nuclei of Schwann cells; d, e, varicose axons and/or extensions of ICC.

From Ramón y Cajal 100b)
Figure 20. Figure 20.

Guinea pig ileum; transverse section of entire circular muscle layer. A single layer of cells (sd; small, dense cells) forms inner subdivision of circular muscle. Below this, elements of deep muscular plexus are present. Scale, 5 μm.

From Gabella 59
Figure 21. Figure 21.

Cytoarchitecture of inner part of circular muscle coat (small intestine). IL, inner layer; OL, outer layer; SC, Schwann cells. ICC DMP (ICC III) in close contact with axonal varicosities of the deep muscular plexus and connected with other ICC as well as with OL (but not IL) by numerous, large nexus junctions (N).
Figure 22. Figure 22.

Mouse small intestine. As many as 8 nexuses (arrows) connect ICC DMP (right) with cells of outer, circular muscle layer (middle and left). Scale, 1 μm.

From Rumessen et al. 105
Figure 23. Figure 23.

Mouse small intestine, deep muscular plexus. OL, IL, outer and inner layers of circular muscle; IC, ICC DMP: F, fibroblast‐like cell; M, macrophage‐like cell. Interstices and cell surfaces are stained with ruthenium red. Axon bundle is completely covered by processes of ICC DMP, which are interconnected by nexuses (arrows). At least 10 axonal varicosities are in intimate contact with ICC DMP. Scale, 1 μm.

From Rumessen et al. 105
Figure 24. Figure 24.

Mouse small intestine, deep muscular plexus. Strong adherence of vesiculated varicosities to ICC DMP is indicated. Interstices are artificially dilated due to excessive perfusion pressure during vascular fixation. However, despite dilation of interstices, varicosities preserve large areas of contact with ICC DMP but not with other neighboring cells. Scale, 1 μm.

From Rumessen et al. 105
Figure 25. Figure 25.

Mouse small intestine. Survey of deep muscular plexus (only part of axons are stained) and ICC DMP (cells with dark cytoplasm), as revealed by ZIO staining. Scale, 50 μm.

From Rumessen and Thuneberg 104
Figure 26. Figure 26.

Mouse small intestine. ICC DMP (IC) in synaptic contact with axonal varicosity (AV), containing small agranular vesicles and larger granular vesicles (cholinergic type). Note presynaptic densities and slightly increased density of postsynaptic membrane. ICC has basal lamina (arrows), which is similar to basal lamina of the adjacent muscle cells (IL, inner circular layer). Scale, 0.5 μm.

From Rumessen et al. 105
Figure 27. Figure 27.

Mouse small intestine. ICC CM in interstices of outer, main layer of circular muscle. Cell processes are in contact with axon bundle (below) and with smooth muscle cells, but synaptic specializations and nexuses are seldom seen in this location. Note absence of caveolae in ICC CM (cf. Figs. 22 and 24). Scale, 1 μm.

Micrograph courtesy of J. J. Rumessen
Figure 28. Figure 28.

Human esophagus. Diagram showing distribution of ICC: in connective tissue septa (I), at periphery of muscular bundles (II), and accompanying nerves within a muscular bundle (III). Arrows, exact locations of groups. ICC of groups II and III contact each other and muscle cells, as well as axons.

From Faussone‐Pellegrini and Cortesini 50
Figure 29. Figure 29.

Human esophageal body, middle third. An ICC (group III; see Fig. 28) contacts smooth muscle cells by close appositions of membranes (arrows) as well as by intermediate‐type and gap junctions (boxed area: insets A,B). Axons (asterisks) are in contact with ICC. Scale, 0.5 μm.

From Faussone‐Pellegrini and Cortesini 50
Figure 30. Figure 30.

Opossum esophageal body. ICC (IC) in circular muscle is connected by gap junction (GJ) to adjacent smooth muscle cell. ICC is in close contact with axons (AX) and innervated (close, gap width <23 nm) by a varicosity, containing mainly small agranular vesicles (SAV). Dense cytoplasm is characterized by accumulations of free ribosomes (long arrow) and profiles of Golgi/endoplasmic reticulum (short arrow). A basal lamina is seen, covering part of the ICC surface. Scale, 0.2 μm.

From Daniel and Posey‐Daniel 31
Figure 31. Figure 31.

Lovebird gizzard. An ICC (IC) forms gap junction (arrow) with smooth muscle cell (Sm). ICC is in contact with bundle of axons (NF), one of which (ax) forms a varicosity with small agranular vesicles.

From Imaizumi and Hama 73
Figure 32. Figure 32.

Rabbit colon. The ICC (c) of taenia coli, associated with small axon bundle (n). Cell contacts several muscle cells (s) by slender processes. Scale, 5 μm.

From Komuro 84
Figure 33. Figure 33.

Rabbit colon. Scanning electron micrographs showing interstitial cells (c1, c2) that overlie a myenteric ganglion (A) and smooth muscle cells (s; B). p, Primary process. Scale, 10 μm.

From Komuro 84
Figure 34. Figure 34.

Rat colon; ZIO stain. ICC (iz) and axons of submuscular plexus (plexus entericus extremus). ICC form a network through contacts between their processes (double arrows), and varicose axons are closely associated with the cells (single arrows). Scale, 50 μm.

From Stach 115
Figure 35. Figure 35.

Mouse colon; ZIO stain. Three stereo pairs of same field, focused on submuscular plexus (A), circular muscle with its nerve supply (B), and Auerbach's plexus (C). Network of ICC is present in association with two nerve plexuses of A and C. Arrows point to corresponding images of ICC. Scale, 20 μm.
Figure 36. Figure 36.

Survey of observations of ICC in various regions of alimentary tract. LM, CM: longitudinal and circular muscle coats. Asterisks, ICC that may be specialized regulatory cells, as judged mainly from morphological studies of an intercalation of these cells between nerves and effector cells. Densities of asterisks reflect densities of ICC in various regions, as reported or suggested from illustrated material. Crosses, ICC of fibroblast‐like ultrastructure, perhaps with mainly supporting functions. Questions marks, data missing or of minor significance. Possibility of interconnections ICC AP/SS and ICC AP/CM/DMP in small intestine is indicated by dotted lines. Also, question of species variation in structure of colonic circular muscle is included.


Figure 1.

Rat ileocecal junction. Ganglionic collar was suggested to represent a local specialization of Auerbach's plexus, with intermediate cells (ICC AP) interposed between ganglion cells and muscle cells.

From Keith 80


Figure 2.

Rabbit intestine; vital staining with methylene blue. Interstitial cells (ICC AP) associated with Auerbach's plexus.

From Ramón y Cajal 100b)


Figure 3.

Guinea pig small intestine; vital staining with methylene blue. ICC AP plexus partly associated with a nerve fascicle (A) and a ganglion (B) of Auerbach's plexus. Scale, 50 μm.

From Taxi 121


Figure 4.

Cat ileum. ICC (arrows) in circular muscle coat. Number and appearance of cells suggest that they are located between the two subdivisions of circular muscle coat (ICC DMP). Scale, 100 μm.

From Vajda and Fehér 128


Figure 5.

Diagrammatic representation of muscularis externa of mouse small intestine. Three types of ICC are depicted: ICC AP (ICC I) associated with Auerbach's plexus (AP) in interval between the longitudinal muscle coat (LM) and outer lamina of circular muscle (CM‐OL); ICC SS (ICC II), unassociated with neural elements in interval between mesothelium (M) and LM; ICC DMP (ICC III), associated with deep muscular plexus (plexus muscularis profundus, PMP) in interval between outer and inner laminae of circular muscle (CM‐OL, CM‐IL). At all three levels ICC contact and envelop macrophage‐like cells (MLC). As a fourth type of ICC (ICC CM), cells with fibroblast features, which accompany nerve fascicles in interstices of CM‐OL, may be distinguished. ICC CM not shown in diagram.

From Thuneberg 124


Figure 6.

Mouse small intestine; stained with methylene blue. Contrast is high, in spite of specimen thickness (intact intestine), because of selectivity of methylene blue for ICC AP. Few, scattered longitudinal muscle cells are also stained. Absence of stained ICC AP in lower right corner is not due to absence of ICC AP. Outline of Auerbach's plexus is faintly visible because of a condensation of ICC AP plexus, mainly around primary nerve fascicles. Scale, 0.5 mm.



Figure 7.

Mouse small intestine; whole mount stained with methylene blue. ICC AP plexus with complex associations of processes. Cell with broad, flat processes (upper right corner) is embracing a ganglion. C, capillary. Scale, 25 μm.



Figure 8.

Cat small intestine. Area between longitudinal (L) and circular (C) muscle coats. Cells marked II, with oval nuclei (N), and interconnected by desmosome‐like junctions (small arrows), may correspond to ICC AP of mouse small intestine. A, axon; large arrows, basal lamina of muscle cells. Scale, 1 μm.

From Taylor et al. 122


Figure 9.

Mouse small intestine. Section tangential to ICC AP plexus. A: ICC AP (with dark cytoplasm after methylene blue staining) are enveloping an MLC. SM, smooth muscle cells of both layers. B and C: cytoplasmic details of ICC AP processes (area between arrows in A). Note interdigitation of processes, numerous mitochondria, presence of gap junctions between ICC AP (arrows), dominance of thin filaments in narrow processes, intermediate filaments in broader processes, and caveolae with associated smooth cisternae. Scale, 5 μm (A), 0.5 μm (B and C).

From Thuneberg 124


Figure 10.

Mouse small intestine. ICC AP (IC) process with highly developed smooth endoplasmic reticulum, forming subsurface cisternae close to caveolae, similar to arrangement in smooth muscle cells (SM). A basal lamina is present (arrows). Scale, 1 μm.

Micrograph courtesy of H. B. Mikkelsen


Figure 11.

Mouse small intestine. Four vesiculated axonal varicosities (arrows) of small (tertiary) fascicle, in close contact with ICC AP (IC), SM, smooth muscle cells. Scale, 0.5 μm.



Figure 12.

Mouse small intestine. Fluorescence micrographs of MLC after uptake of fluorescein‐labeled dextran. Ramified cells in focus, MLC between the longitudinal and circular muscle layers. Out of focus: subserous MLC, forming longitudinal rows. Note lack of connections between MLC and (in A) association of MLC with faintly visible Auerbach's plexus and with capillaries. Scale, 100 μm (A), 25 μm (B).

From Mikkelsen et al. 95


Figure 13.

Mouse small intestine; isolated musculature stained with methylene blue. Circular muscle layer has been partially separated from longitudinal muscle and bent back along oblique line. ICC AP remain associated with longitudinal muscle layer (lighter triangular area). Scale, 100 μm.

From Thuneberg et al. 126


Figure 14.

Mouse small intestine. Intracellular records of electrical activity, all from same intestinal preparation, which is incubated in a medium with added methylene blue. A: unstained area. B, C, D, and inset: area with selectively stained ICC AP (cf. Fig. 7), at time 10 min (B), 27 min (C), and 33 min (D) after sacrifice of animal. Arrow: He‐Ne laser on. Inset: impalement of another cell after 2‐min illumination. Laser illumination had no effect on slow waves in areas where ICC AP were unstained. Scales, 20 mV and 10 s.

From Thuneberg et al. 125


Figure 15.

Mouse small intestine; methylene blue staining of ICC AP and contraction nodes of smooth muscle cells (longitudinal muscle coat). Note correspondence between positions of ICC AP processes and contraction nodes. Scale, 50 μm.

From Thuneberg 124


Figure 16.

Mouse small intestine. Isolated musculature grown in tissue culture for a few days. Rim of tissue expiant at top right; from this has grown a bundle of parallel, ribbon‐shaped smooth muscle cells (SM, longitudinal axis indicated). N, nucleus of ramified, spontaneously contractile cell (ICC?), contacting several smooth muscle cells and connected by long, contractile process (arrows) to cells of expiant. Scale, 25 μm.



Figure 17.

Direct (left) and indirect (right) neural control of smooth muscle. 1) Axons; 2 and 3) intercalated cells of two types: a fibroblast‐like cell (2) and a macrophage‐like cell (3); 4) smooth muscle cell.

From Feyrter 52


Figure 18.

Mouse duodenum. ICC(AP) extending through entire thickness of longitudinal muscle. CAP, lumen of capillary between muscle layers. SER, serosal surface. ICC contacts two processes with ultrastructural characteristics of ICC SS. Scale, 5 μm.

Micrograph courtesy of J. J. Rumessen


Figure 19.

Guinea pig small intestine; Golgi method. Deep muscular plexus or plexus muscularis profundus (B, right) with associated ICC DMP (A, left). Meshes of plexus, and ICC, are elongated in direction parallel to cells of circular muscle (top to bottom); a, b, f, ICC; c, positions of unstained nuclei of Schwann cells; d, e, varicose axons and/or extensions of ICC.

From Ramón y Cajal 100b)


Figure 20.

Guinea pig ileum; transverse section of entire circular muscle layer. A single layer of cells (sd; small, dense cells) forms inner subdivision of circular muscle. Below this, elements of deep muscular plexus are present. Scale, 5 μm.

From Gabella 59


Figure 21.

Cytoarchitecture of inner part of circular muscle coat (small intestine). IL, inner layer; OL, outer layer; SC, Schwann cells. ICC DMP (ICC III) in close contact with axonal varicosities of the deep muscular plexus and connected with other ICC as well as with OL (but not IL) by numerous, large nexus junctions (N).



Figure 22.

Mouse small intestine. As many as 8 nexuses (arrows) connect ICC DMP (right) with cells of outer, circular muscle layer (middle and left). Scale, 1 μm.

From Rumessen et al. 105


Figure 23.

Mouse small intestine, deep muscular plexus. OL, IL, outer and inner layers of circular muscle; IC, ICC DMP: F, fibroblast‐like cell; M, macrophage‐like cell. Interstices and cell surfaces are stained with ruthenium red. Axon bundle is completely covered by processes of ICC DMP, which are interconnected by nexuses (arrows). At least 10 axonal varicosities are in intimate contact with ICC DMP. Scale, 1 μm.

From Rumessen et al. 105


Figure 24.

Mouse small intestine, deep muscular plexus. Strong adherence of vesiculated varicosities to ICC DMP is indicated. Interstices are artificially dilated due to excessive perfusion pressure during vascular fixation. However, despite dilation of interstices, varicosities preserve large areas of contact with ICC DMP but not with other neighboring cells. Scale, 1 μm.

From Rumessen et al. 105


Figure 25.

Mouse small intestine. Survey of deep muscular plexus (only part of axons are stained) and ICC DMP (cells with dark cytoplasm), as revealed by ZIO staining. Scale, 50 μm.

From Rumessen and Thuneberg 104


Figure 26.

Mouse small intestine. ICC DMP (IC) in synaptic contact with axonal varicosity (AV), containing small agranular vesicles and larger granular vesicles (cholinergic type). Note presynaptic densities and slightly increased density of postsynaptic membrane. ICC has basal lamina (arrows), which is similar to basal lamina of the adjacent muscle cells (IL, inner circular layer). Scale, 0.5 μm.

From Rumessen et al. 105


Figure 27.

Mouse small intestine. ICC CM in interstices of outer, main layer of circular muscle. Cell processes are in contact with axon bundle (below) and with smooth muscle cells, but synaptic specializations and nexuses are seldom seen in this location. Note absence of caveolae in ICC CM (cf. Figs. 22 and 24). Scale, 1 μm.

Micrograph courtesy of J. J. Rumessen


Figure 28.

Human esophagus. Diagram showing distribution of ICC: in connective tissue septa (I), at periphery of muscular bundles (II), and accompanying nerves within a muscular bundle (III). Arrows, exact locations of groups. ICC of groups II and III contact each other and muscle cells, as well as axons.

From Faussone‐Pellegrini and Cortesini 50


Figure 29.

Human esophageal body, middle third. An ICC (group III; see Fig. 28) contacts smooth muscle cells by close appositions of membranes (arrows) as well as by intermediate‐type and gap junctions (boxed area: insets A,B). Axons (asterisks) are in contact with ICC. Scale, 0.5 μm.

From Faussone‐Pellegrini and Cortesini 50


Figure 30.

Opossum esophageal body. ICC (IC) in circular muscle is connected by gap junction (GJ) to adjacent smooth muscle cell. ICC is in close contact with axons (AX) and innervated (close, gap width <23 nm) by a varicosity, containing mainly small agranular vesicles (SAV). Dense cytoplasm is characterized by accumulations of free ribosomes (long arrow) and profiles of Golgi/endoplasmic reticulum (short arrow). A basal lamina is seen, covering part of the ICC surface. Scale, 0.2 μm.

From Daniel and Posey‐Daniel 31


Figure 31.

Lovebird gizzard. An ICC (IC) forms gap junction (arrow) with smooth muscle cell (Sm). ICC is in contact with bundle of axons (NF), one of which (ax) forms a varicosity with small agranular vesicles.

From Imaizumi and Hama 73


Figure 32.

Rabbit colon. The ICC (c) of taenia coli, associated with small axon bundle (n). Cell contacts several muscle cells (s) by slender processes. Scale, 5 μm.

From Komuro 84


Figure 33.

Rabbit colon. Scanning electron micrographs showing interstitial cells (c1, c2) that overlie a myenteric ganglion (A) and smooth muscle cells (s; B). p, Primary process. Scale, 10 μm.

From Komuro 84


Figure 34.

Rat colon; ZIO stain. ICC (iz) and axons of submuscular plexus (plexus entericus extremus). ICC form a network through contacts between their processes (double arrows), and varicose axons are closely associated with the cells (single arrows). Scale, 50 μm.

From Stach 115


Figure 35.

Mouse colon; ZIO stain. Three stereo pairs of same field, focused on submuscular plexus (A), circular muscle with its nerve supply (B), and Auerbach's plexus (C). Network of ICC is present in association with two nerve plexuses of A and C. Arrows point to corresponding images of ICC. Scale, 20 μm.



Figure 36.

Survey of observations of ICC in various regions of alimentary tract. LM, CM: longitudinal and circular muscle coats. Asterisks, ICC that may be specialized regulatory cells, as judged mainly from morphological studies of an intercalation of these cells between nerves and effector cells. Densities of asterisks reflect densities of ICC in various regions, as reported or suggested from illustrated material. Crosses, ICC of fibroblast‐like ultrastructure, perhaps with mainly supporting functions. Questions marks, data missing or of minor significance. Possibility of interconnections ICC AP/SS and ICC AP/CM/DMP in small intestine is indicated by dotted lines. Also, question of species variation in structure of colonic circular muscle is included.

 1. Ambache, N., H. C. Brummer, J. Whiting, and M. Wood. Atropine‐resistant substances in extracts of plexus‐containing longitudinal muscle (PC‐LM) from guinea‐pig ileum. J. Physiol. Lond. 186: 32P–33P, 1966.
 2. Anuras, S., J. Christensen, and A. R. Cooke. A comparison of intrinsic nerve supplies of two muscular layers of duodenum. Am. J. Physiol. 233 (Endocrinol. Metab. Gastrointest. Physiol. 2): E28–E31, 1977.
 3. Arthur, R. P., and W. B. Shelley. The technology of in vitro staining of nerves in human skin with thiazin dyes. J. Invest. Dermatol. 33: 121–144, 1959.
 4. Barbosa, P., and T. M. Peters. The effects of vital dyes on living organisms with special reference to methylene blue and neutral red. Histochem. J. 3: 71–93, 1971.
 5. Bass, P. Electrophysiology of intestinal smooth muscle. In: Handbook of Physiology. Alimentary Canal. Motility, edited by C. F. Code. Washington, DC: Springer‐Verlag, 1968, sect. 6, vol. IV, chapt. 100, p. 2051–2074.
 6. Boeke, J. The problem of interstitial cells in the nervous endformation. Proc. K. Ned. Akad. Wet. Ser. C Biol. Med. Sci. 45: 208–214, 1942.
 7. Boeke, J. The sympathetic endformation, its synaptology, the interstitial cells, the periterminal network, and its bearing on the neurone theory. Discussion and critique. Acta Anat. 8: 18–61, 1949.
 8. Bortoff, A. Electrical transmission of slow waves from longitudinal to circular intestinal muscle. Am. J. Physiol. 209: 1254–1260, 1965.
 9. Bortoff, A. Myogenic control of intestinal motility. Physiol. Rev. 56: 418–434, 1976.
 10. Bortoff, A., and E. Ghalib. Temporal relationship between electrical and mechanical activity of longitudinal and circular muscle during intestinal peristalsis. Am. J. Dig. Dis. 17: 317–325, 1972.
 11. Bortoff, A., D. Michaels, and P. Mistretta. Dominance of longitudinal muscle in propagation of intestinal slow waves. Am. J. Physiol. 240 (Cell Physiol. 9): C135–C147, 1981.
 12. Botár, J. The Autonomic Nervous System. An Introduction to its Physiological and Pathological Histology. Budapest: Akad. Kiadó, 1966.
 13. Cai, W.‐Q., and G. Gabella. Structure and innervation of the musculature at the gastroduodenal junction of the guinea‐pig. J. Anat. 139: 93–104, 1984.
 14. Caprilli, R., G. Frieri, and P. Vernia. Electrophysiology of intestinal smooth muscle. In: Handbook of Experimental Pharmacology. Mediators and Drugs in Gastrointestinal Motility. Morphological Basis and Neurophysiological Control, edited by G. Bertaccini. Berlin: Springer‐Verlag, 1982, vol. 59, pt. 1, chapt. 5, p. 117–143.
 15. Chambers, M. M., Y. J. Kingma, and K. L. Bowes. Intracellular electrical activity in circular muscle of canine colon. Gut 25: 1268–1270, 1984.
 16. Chamley‐Campbell, J., G. R. Campbell, and R. Ross. The smooth muscle cell in culture. Physiol. Rev. 59: 1–61, 1979.
 17. Cheung, D. W., and E. E. Daniel. Comparative study of the smooth muscle layers of the rabbit duodenum. J. Physiol. Lond. 309: 13–27, 1980.
 18. Christensen, J., R. Caprilli, and G. F. Lund. Electrical slow waves in circular muscle in cat colon. Am. J. Physiol. 222: 771–776, 1969.
 19. Clara, M. Wo steht die Morphologie der neurovegetativen Peripherie. Acta Neuroveg. Suppl. 6: 1–17, 1955.
 20. Connor, J. A. On exploring the basis for slow potential oscillations in the mammalian stomach and intestine. J. Exp. Biol. 81: 153–173, 1979.
 21. Connor, J. A., D. Kreulen, C. L. Prosser, and R. Weigel. Interaction between longitudinal and circular muscle in intestine of cat. J. Physiol. Lond. 273: 665–689, 1977.
 22. Connor, J. A., A. W. Mangel, and B. Nelson. Propagation and entrainment of slow waves in cat small intestine. Am. J. Physiol. 237 (Cell Physiol. 6): C237–C246, 1979.
 23. Connor, J. A., C. L. Prosser, and W. A. Weems. A study of pace‐maker activity in intestinal smooth muscle. J. Physiol. Lond. 240: 671–701, 1974.
 24. Cook, R. D., and G. Burnstock. The ultrastructure of Auerbach's plexus in the guinea pig. II. Non‐neuronal elements. J. Neurocytol. 5: 195–206, 1976.
 25. Daniel, E. E. Nerves In: Nerves and the Gut, edited by F. P. Brooks and P. W. Evers. New York: Slack, 1977, p. 154–196.
 26. Daniel, E. E., J. Crankshaw, and S. Sarna. Prostaglandins and tetrodotoxin‐insensitive relaxation of opossum lower esophageal sphincter. Am. J. Physiol. 236 (Endocrinol. Metab. Gastrointest. Physiol. 5): E153–E172, 1979.
 27. Daniel, E. E., A. Helmy‐Elkholy, L. P. Jager, and M. S. Kannan. Neither a purine nor VIP is the mediator of inhibitory nerves of opossum oesophageal smooth muscle. J. Physiol. Lond. 336: 243–260, 1983.
 28. Daniel, E. E., and V. Posey‐Daniel. Effects of scorpion venom on structure and function of esophageal lower sphincter (LES) and body circular muscle (BCM) from opossum. Can. J. Physiol. Pharmacol. 62: 360–373, 1984.
 29. Daniel, E. E., and V. Posey‐Daniel. Neuromuscular structures in opossum esophagus: role of interstitial cells of Cajal. Am. J. Physiol. 246 (Gastrointest. Liver Physiol. 9): G305–G315, 1984.
 30. Daniel, E. E., Y. Sakai, J. E. T. Fox, and V. Posey‐Daniel. Structural basis for function of circular muscle of canine corpus. Can. J. Physiol. Pharmacol. 62: 1304–1314, 1984.
 31. Daniel, E. E., and S. Sarna. The generation and conduction of activity in smooth muscle. Annu. Rev. Pharmacol. Toxicol. 18: 145–166, 1978.
 32. Daniel, E. E., G. S. Taylor, V. P. Daniel, and M. E. Holman. Can nonadrenergic inhibitory varicosities be identified structurally. Can. J. Physiol. Pharmacol. 55: 243–250, 1977.
 33. Debski, L., K. L. Bowes, Y. J. Kingma, and R. Gill. Electrophysiology of intestinal smooth muscle. In: Gastrointestinal Motility, edited by C. Roman. Lancaster, UK: MTP, 1984, p. 397–403. (Proc. Int. Symp. Gastrointest. Motil., 9th, Aix‐en‐Provence, France, 1983.).
 34. Dixon, J. S., and J. A. Gosling. Electron microscopic observations on the renal caliceal wall in the rat. Z. Zellforsch. Mikrosk. Anat. 103: 328–340, 1970.
 35. Dixon, J. S., and J. A. Gosling. The fine structure of pacemaker cells in the pig renal calices. Anat. Rec. 175: 139–154, 1973.
 36. Duchon, G., R. Henderson, and E. E. Daniel. Circular muscle layers in the small intestine. In: Proc. Int. Symp. Gastrointest. Motil., 4th, Banff, Alberta, Canada, 1973, edited by E. E. Daniel. Vancouver, Canada: Mitchell, 1974, p. 635–646.
 37. Durdle, N. G., Y. J. Kingma, and K. L. Bowes. Electrophysiology of intestinal smooth muscle. In: Motility of the Digestive Tract, edited by M. Wienbeck. New York: Raven, 1982, p. 483–489. (Proc. Int. Symp. Gastrointest. Motil., 8th, Königstein, FRG, 1981.).
 38. Durdle, N. G., Y. J. Kingma, K. L. Bowes, and M. M. Chambers. Origin of slow waves in the canine colon. Gastroenterology 84: 375–382, 1983.
 39. Elden, L., and A. Bortoff. Electrical coupling of longitudinal and circular intestinal muscle. Am. J. Physiol. 246 (Gastrointest. Liver Physiol. 9): G618–G626, 1984.
 40. El‐Sharkawy, T. Y., B. L. Bardakjian, W. M. MacDonald, and N. E. Diamant. Origins of the multiple patterns of electrical control activity in the colon. In: Motility of the Digestive Tract. edited by M. Wienbeck. New York: Raven, 1982, p. 491–497. (Proc. Int. Symp. Gastrointest. Motil., 8th, Königstein, FRG, 1981.).
 41. Fahrenkrug, J. Vasoactive polypeptide: measurement, distribution and putative neurotransmitter function. Digestion 19: 149–169, 1979.
 42. Faussone‐Pellegrini, M. S. Le caratteristiche ultrastrutturali della tunica muscolare dell'ileo e del colon di ratto. A: porzione interna dello strato circolare. Arch. Ital. Anat. Embriol. 88: 25–40, 1983.
 43. Faussone‐Pellegrini, M. S. Morphogenesis of the special circular muscle layer and of the interstitial cells of Cajal related to the plexus muscularis profundus of mouse intestinal muscle coat. An E. M. study. Anat. Embryol. 169: 151–158, 1984.
 44. Faussone‐Pellegrini, M. S. Cytodifferentiation of the interstitial cells of Cajal related to the myenteric plexus of mouse intestinal muscle coat. An E. M. study from foetal to adult life. Anat. Embryol. 174: 163–169, 1985.
 45. Faussone‐Pellegrini, M. S. Ultrastructural pecularities of the inner portion of the circular layer of the colon. II. Research on the mouse. Acta Anat. 122: 187–192, 1985.
 46. Faussone‐Pellegrini, M. S., and C. Cortesini. Some ultrastructural features of the muscular coat of human small intestine. Acta Anat. 115: 47–68, 1983.
 47. Faussone‐Pellegrini, M. S., and C. Cortesini. Ultrastructural pecularities of the inner portion of the circular layer of colon. I. Research in the human. Acta Anat. 120: 185–189, 1984.
 48. Faussone‐Pellegrini, M. S., and C. Cortesini. Ultrastructural features and localization of the interstitial cells of Cajal in the smooth muscle coat of human esophagus. J. Submicrosc. Cytol. 17: 187–197, 1985.
 49. Faussone‐Pellegrini, M. S., C. Cortesini, and P. Romagnoli. Sull'ultrastruttura della tunica muscolare della porzione cardiale dell'esofago e dello stomaco umano con particolare riferimento alle cosiddette cellule interstiziali di Cajal. Arch. Ital. Anat. Embriol. 82: 157–177, 1977.
 50. Feyrter, F. Über die Pathologie der vegetativen nervösen Peripherie und ihrer ganglionären Regulationsstätten. Vienna: Mandrich, 1951.
 51. Fox, D. A., and P. Bass. Selective myenteric neuronal denervation of the rat jejunum. Differential control of the propagation of migrating myoelectric complex and basic electric rhythm. Gastroenterology 87: 572–577, 1984.
 52. Furness, J. B., and M. Costa. Types of nerves in the enteric nervous system. Neuroscience 5: 1–20, 1980.
 53. Furness, J. B., and M. Costa. Electrophysiology of intestinal smooth muscle. In: Handbook of Experimental Pharmacology. Mediators and Drugs in Gastrointestinal Motility. I. Morphological Basis and Neurophysiological Control, edited by G. Bertaccini. Berlin: Springer‐Verlag, 1982, vol. 59, pt. 1, chapt. 11, p. 383–462.
 54. Gabella, G. Innervation of the intestinal muscular coat. J. Neurocytol. 1: 341–362, 1972.
 55. Gabella, G. Intercellular junctions between circular and longitudinal intestinal muscle layers. Z. Zellforsch. Mikrosk. Anat. 125: 191–199, 1972.
 56. Gabella, G. Special muscle cells and their innervation in the mammalian small intestine. Cell Tissue Res. 153: 63–77, 1974.
 57. Gabella, G. Innervation of the gastrointestinal tract. Int. Rev. Cytol. 59: 129–193, 1979.
 58. Gabella, G. Chicken gizzard. The muscle, the tendon and their attachment. Anat. Embryol. 171: 151–162, 1985.
 59. Gabella, G. Structure of the musculature of the chicken small intestine. Anat. Embryol. 171: 139–149, 1985.
 60. Gabella, G., and D. Blundell. Gap junctions of the muscles of the small and large intestine. Cell Tissue Res. 219: 469–488, 1981.
 61. Gershon, M. D., and S. Bursztajn. Properties of the enteric nervous system: limitation of access of intravascular macro‐molecules to the myenteric plexus and muscularis externa. J. Comp. Neurol. 180: 467–488, 1978.
 62. Gibbins, I. L. Lack of correlation between ultrastructural and pharmacological types of non‐adrenergic autonomic nerves. Cell Tissue Res. 221: 551–581, 1982.
 63. Gillespie, J. S. Electrophysiology of intestinal smooth muscle. In: Motility of the Digestive Tract, edited by M. Wienbeck. New York: Raven, 1982, p. 51–66. (Proc. Int. Symp. Gastrointest. Motil., 8th, Königstein, FRG, 1981.).
 64. Henderson, R. M., G. Duchon, and E. E. Daniel. Cell contacts in duodenal smooth muscle layers. Am. J. Physiol. 221: 564–574, 1971.
 65. Hirst, G. D. S. Mechanisms of peristalsis. Br. Med. Bull. 35: 263–268, 1979.
 66. Hirst, G. D. S., M. E. Holman, and H. C. McKirdy. Two descending nerve pathways activated by distension of guinea‐pig small intestine. J. Physiol. Lond. 244: 113–127, 1975.
 67. Hirst, G. D. S., and H. C. McKirdy. A nervous mechanism for descending inhibition in guinea‐pig small intestine. J. Physiol. Lond. 238: 129–143, 1974.
 68. Hirst, G. D. S., and H. C. McKirdy. Synaptic potentials recorded from neurones of the submucous plexus of guinea‐pig small intestine. J. Physiol. Lond. 249: 369–385, 1975.
 69. Holman, M. E. The intrinsic innervation and peristaltic reflex of the small intestine. Smooth Muscle: An Assessment of Current Knowledge, edited by E. Bülbring, A. F. Brading, A. W. Jones, and T. Tomita. London: Arnold, 1981, p. 311–338.
 70. Huizinga, J. D., N. E. Diamant, and T. Y. El‐Sharkawy. Electrical basis of contractions in the muscle layers of the pig colon. Am. J. Physiol. 245 (Gastrointest. Liver Physiol. 8): G482–G491, 1983.
 71. Imaizumi, M., and K. Hama. An electron microscopic study on the interstitial cells of the gizzard in the love‐bird (Uroloncha domestica). Z. Zellforsch. Mikrosk. Anat. 97: 351–357, 1969.
 72. Jabonero, V. Die Interstitiellen Zellen des vegetativen Nervensystems und ihre vermutliche Analogie zu anderen Elementen. I. Acta Neuroveg. 5: 1–24, 1953.
 73. Jabonero, V. Die Interstitiellen Zellen des vegetativen Nervensystems und ihre vermutliche Analogie zu anderen Elementen. II. Acta Neuroveg. 5: 266–280, 1953.
 74. Jabonero, V. Die plexiforme Synapse auf Distanz und die Bedeutung der sogenannten interkalären Zellen. Acta Neuroveg. 19: 276–302, 1959.
 75. Jager, L. P., J. Jury, and E. E. Daniel. Electrophysiology of intestinal smooth muscle. In: Gastrointestinal Motility, edited by C. Roman. Lancaster, UK: MTP, 1984, p. 9–16. (Proc. Int. Symp. Gastrointest. Motil., 9th, Aix‐en‐Provence, France, 1983.).
 76. Jessen, K. R., and R. Mirsky. Glial fibrillary acidic polypeptides in peripheral glia. Molecular weight, heterogeneity and distribution. J. Neuroimmunol. 8: 377–393, 1985.
 77. Kappers, J. A. A survey of different opinions relating to the structure of the peripheral autonomic nervous system. Acta Neuroveg. 26: 145–171, 1964.
 78. Keith, A. An account of six specimens of the great bowel removed by operation: with some observations on the motor mechanism of the colon. Br. J. Surg. 2: 576–599, 1915.
 79. Keith, A. A new theory of the causation of enterostasis. Lancet 2: 371–375, 1915.
 80. Keith, A. Proceedings of the Anatomical Society of Great Britain and Ireland. J. Anat. Physiol. 50: 1P–3P, 1916.
 81. Kobayashi, M., C. L. Prosser, and T. Nagai. Electrical properties of intestinal muscle as measured intracellularly and extracellularly. Am. J. Physiol. 213: 275–286, 1967.
 82. Komuro, T. The interstitial cells in the colon of the rabbit. Cell Tissue Res. 222: 41–51, 1982.
 83. Kyi, J. K. K., and E. E. Daniel. The effects of ischemia on intestinal nerves and electrical slow waves. Am. J. Digest. Dis. 15: 959–981, 1970.
 84. Leek, B. F. Electrophysiology of intestinal smooth muscle. In: Handbook of Sensory Physiology. Enteroceptors, edited by E. Neil. Berlin: Springer‐Verlag, 1972, vol. III, pt. 1, p. 113–129.
 85. Leeuwe, H. Over de interstitieele cel (Cajal) Holland: Univ. of Utrecht, 1937.
 86. Li, P.‐L. Neue Beobachtungen über die Struktur des Zirkulärmuskels im Dünndarm bei Wirbeltieren. Eine vergleichende Studie. Z. Anat. Entwicklungsgesch. 107: 212–222, 1937.
 87. Li, P.‐L. The intramural nervous system of the small intestine with special reference to the innervation of the inner subdivision of its circular muscle. J. Anat. 74: 348–359, 1940.
 88. Magnus, R. Versuche am überlebenden Dünndarm von Säugetieren. II. Mitteilung. Die Beziehungen des Darmnervensystems zur automatischen Darmbewegung. Pflüegers Arch. Gesamte Physiol. Menschen Tiere 102: 349–363, 1904.
 89. Mangel, A. W., J. A. Connor, and C. L. Prosser. Effects of alterations in calcium levels on cat small intestinal slow waves. Am. J. Physiol. 243 (Cell Physiol. 12): C7–C13, 1982.
 90. McGill, C. The structure of smooth muscle in the resting and in the contracted condition. Am. J. Anat. 9: 493–545, 1909.
 91. Merwyk, A. J. van, and H. L. Duthie. Electrophysiology of intestinal smooth muscle. In: Gastrointestinal Motility, edited by J. Christensen. New York: Raven, 1980, p. 473–478. (Proc. Int. Symp. Gastrointest. Motil., 7th, Iowa City, Iowa, 1979.).
 92. Meyling, H. A. Structure and significance of the peripheral extension of the autonomic nervous system. J. Comp. Neurol. 99: 495–543, 1953.
 93. Mikkelsen, H. B., L. Thuneberg, J. J. Rumessen, and N. Thorball. Macrophage‐like cells in the muscularis externa of mouse small intestine. Anat. Rec. 213: 77–86, 1985.
 94. Nicaise, G. The gliointerstitial system of molluscs. Int. Rev. Cytol. 34: 251–332, 1973.
 95. Ono, M. Electron microscopic observations on the ganglia of Auerbach's plexus and autonomic nerve endings in muscularis externa of the mouse small intestine. Sapporo Med. J. 32: 56–74, 1967.
 96. Publicover, N. G., and K. M. Sanders. A technique to locate the pacemaker in smooth muscles. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 57: 1586–1590, 1984.
 97. Purves, R. D. Muscarinic excitation: a microelectrophoretic study on cultured smooth muscle cells. Br. J. Pharmacol. 52: 77–86, 1974.
 98. Purves, R. D., G. E. Mark, and G. Burnstock. The electrical activity of single isolated smooth muscle cells. Pfluegers Arch. 341: 325–330, 1973.
 99. Ramón y Cajal, S. Sur les ganglions et plexus nerveux de l'intestin. Compt. Rend. Soc. Biol. Paris 45: 217–223, 1893.
 100. Ramón y Cajal, S. Histologie du système nerveux de l'Homme et des Vertébrés. Paris: Maloine, 1911.
 101. Richardson, K. C. Electronmicroscopic observations on Auerbach's plexus in the rabbit, with special reference to the problem of smooth muscle innervation. Am. J. Anat. 103: 99–136, 1958.
 102. Richardson, K. C. Studies on the structure of autonomic nerves in the small intestine, correlating the silver‐impregnated image in light microscopy with the permanganate‐fixed ultrastructure in electron microscopy. J. Anat. 94: 457–472, 1960.
 103. Rogers, D. C., and G. Burnstock. The interstitial cell and its place in the concept of the autonomic ground plexus. J. Comp. Neurol. 126: 255–284, 1966.
 104. Rumessen, J. J., and L. Thuneberg. Plexus muscularis profundus and associated interstitial cells. I. Light microscopical studies of mouse small intestine. Anat. Rec. 203: 115–127, 1982.
 105. Rumessen, J. J., L. Thuneberg, and H. B. Mikkelsen. Plexus muscularis profundus and associated interstitial cells. II. Ultrastructural studies of mouse small intestine. Anat. Rec. 203: 129–146, 1982.
 106. Sanders, K. M. Endogenous prostaglandin E and contractile activity of isolated ileal smooth muscle. Am. J. Physiol. 234 (Endocrinol. Metab. Gastrointest. Physiol. 3): E209–E212, 1978.
 107. Sanders, K. M. Evidence that prostaglandins are local regulatory agents in canine ileal circular muscle. Am. J. Physiol. 246 (Gastrointest. Liver Physiol. 9): G361–G371, 1984.
 108. Sanders, K. M. Role of prostaglandins in regulating gastric motility. Am. J. Physiol. 247 (Gastrointest. Liver Physiol. 10): G117–G126, 1984.
 109. Sanders, K. M., and T. E. Northrup. Prostaglandin synthesis by microsomes of circular and longitudinal gastrointestinal muscles. Am. J. Physiol. 244 (Gastrointest. Liver Physiol. 7): G442–G448, 1983.
 110. Schabadasch, A. Intramurale Nervengeflechte des Darmrohrs. Z. Zellforsch. Mikrosk. Anat. 10: 310–385, 1930.
 111. Schabadasch, A. Untersuchungen zur Methodik der Methylenblaufärbung des vegetativen Nervensystems. Z. Zellforsch. Mikrosk. Anat. 10: 221–243, 1930.
 112. Schofield, G. C. Electrophysiology of intestinal smooth muscle. In: Handbook of Physiology. Alimentary Canal. Motility, edited by C. F. Code. Washington, DC: Am. Physiol. Soc., 1968, sect. 6, vol. IV, chapt. 80, p. 1579–1628.
 113. Scott, W. A., N. A. Pawlowski, M. Andreach, and Z. A. Cohn. Resting macrophages produce distinct metabolites from exogenous arachidonic acid. J. Exp. Med. 155: 535–547, 1982.
 114. Stach, W. Neurohistologische Untersuchungen an den Nervengeflechten der Dickdarmwand. Ein Beitrag zur Innervation des Magen‐Darmkanals. Rostock, GDR: Univ. of Rostock, 1969.
 115. Stach, W. Der Plexus entericus extremus des Dickdarmes und seine Beziehungen zu den interstitiellen Zellen (Cajal). Z. Mikrosk. Anat. Forsch. Leipz. 85: 245–272, 1972.
 116. Stöhr, P. Electrophysiology of intestinal smooth muscle. In: Handbuch der mikroskopischen Anatomie des Menschen, edited by W. von Möllendorff. Berlin: Springer‐Verlag, 1928, vol. IV, pt. 1, p. 265–447.
 117. Stöhr, P. Electrophysiology of intestinal smooth muscle. In: Handbuch der mikroskopischen Anatomie des Menschen, edited by W. von Möllendorff and W. Bargmann. Berlin: Springer‐Verlag, 1957, vol. IV, pt 5, p. 1–678.
 118. Suzuki, N., C. L. Prosser, and V. Dahms. Boundary cells between longitudinal and circular layers: essential for electrical slow waves in cat intestine. Am. J. Physiol. 250 (Gastrointest. Liver Physiol. 13): G287–G294, 1986.
 119. Takemura, R., and Z. Werb. Secretory products of macrophages and their physiological functions. Am. J. Physiol. 246 (Cell Physiol. 15): C1–C9, 1984.
 120. Taxi, J. Cellules de Schwann et “cellules interstitielles de Cajal” au niveau des plexus nerveux de la musculeuse intestinale du Cobaye: retour aux definitions. Arch. Anat. Microsc. Morphol. Exp. 41: 281–304, 1952.
 121. Taxi, J. Contribution á l'étude des connexions des neurones moteurs du systeme nerveux autonome. Ann. Sci. Nat. Zool. Biol. Anim. 7: 413–674, 1965.
 122. Taylor, A. B., D. Kreulen, and C. L. Prosser. Electron microscopy of the connective tissues between longitudinal and circular muscle of small intestine of cat. Am. J. Anat. 150: 427–442, 1977.
 123. Taylor, G. S., E. E. Daniel, and T. Tomita. Origin and mechanism of intestinal slow waves. In: Proc. Int. Symp. Gastrointest. Motil., 5th Leuven, Belgium, 1975, edited by G. Vantrappen. Herentals, Belgium: Typoff, 1976, p. 31–36.
 124. Thuneberg, L. Interstitial cells of Cajal: intestinal pacemaker cells. Adv. Anat. Embryol. Cell Biol. 71: 1–130, 1982.
 125. Thuneberg, L., V. Johansen, J. J. Rumessen, and B. G. Andersen. Electrophysiology of intestinal smooth muscle. In: Gastrointestinal Motility, edited by C. Roman. Lancaster, UK: MTP, 1984, p. 495–502. (Proc. Int. Symp. Gastrointest. Motil., 9th, Aix‐en‐Provence, France, 1983.).
 126. Thuneberg, L., J. J. Rumessen, and H. B. Mikkelsen. Electrophysiology of intestinal smooth muscle. In: Motility of the Digestive Tract, edited by M. Wienbeck. New York: Raven, 1982, p. 115–122. (Proc. Int. Symp. Gastrointest. Motil., 8th, Königstein, FRG, 1981.).
 127. Tomita, T. Electrophysiology of intestinal smooth muscle. In: Smooth Muscle: An Assessment of Current Knowledge, edited by E. Bülbring, A. F. Brading, A. W. Jones, and T. Tomita. London: Arnold, 1981, p. 127–156.
 128. Vajda, J., and E. FehéR. Distribution and fine structure of the interstitial cells of Cajal. Acta Morphol. Acad. Sci. Hung. 28: 251–258, 1980.
 129. Yamamoto, M. Electron microscopic studies on the innervation of the smooth muscle and the interstitial cell of Cajal in the small intestine of the mouse and bat. Arch. Histol. Jpn. 40: 171–201, 1977.
References in Addendum
 1. Christensen, J., and G. A. Rick. The intrinsic innervation of the mammalian colon: confirmation of a plexus at the circular muscle‐submucosal interface. J. Autonom. Nerv. Syst. In press.
 2. Christensen, J., G. A. Rick, and D. J. Soll. Intramural nerves and interstitial cells revealed by the Champy‐Maillet stain in the opossum esophagus. J. Autonom. Nerv. Syst. 19: 137–151, 1987.
 3. Cortesini, C., and M. S. Faussone‐Pellegrini. Electrophysiology of intestinal smooth muscle. In: Diseases of the Esophagus, edited by J. R. Siewert and A. H. Hölscher, Berlin, FRG: Springer, 1985, p. 923–927.
 4. Daniel, E. E., L. P. Jager, J. Jury, A. Helmy‐Elkholy, M. S. Cannan, and V. Posey‐Daniel. The mediators and mechanisms causing the non‐adrenergic, non‐cholinergic nerve responses in opossum esophagus: role of interstitial cells of Cajal. Biomed. Res. 5: 67–84, 1984.
 5. Faussone‐Pellegrini, M. S. Cytodifferentiation of the interstitial cells of Cajal of mouse colonic circular muscle layer. An EM study from fetal to adult life. Acta Anat. 128: 98–109, 1987.
 6. Faussone‐Pellegrini, M. S. Comparative study of interstitial cells of Cajal. Acta Anat. 130: 109–126, 1987.
 7. Faussone‐Pellegrini, M. S., and C. Cortesini. The muscle coat of the lower esophageal sphincter in patients with achalasia and hypertensive sphincter. An electron microscopic study. J. Submicrosc. Cytol. 17: 673–685, 1985.
 8. Fox, J. E. T., F. Kostolanska, H. D. Allescher, and E. E. Daniel. Neurotensin and the canine small intestine. 1. Circular muscle motility in vivo and in vitro (Abstract). Digest. Dis. Sci. 32: 910, 1987.
 9. Hara, Y., M. Kubota, and J. H. Szurszewski. Electrophysiology of smooth muscle of the small intestine of some mammals. J. Physiol. Lond. 372: 501–520, 1986.
 10. Kobayashi, S., M. Suzuki, T. Endo, S. Tsuji, and E. E. Daniel. Framework of the enteric nerve plexuses: an immunocytochemical study in the guinea pig jejunum using an antiserum to S‐100 protein. Arch. Histol. Jpn. 49: 159–188, 1986.
 11. Mikkelsen, H. B., R. Mirsky, K. R. Jessen, and L. Thuneberg. Macrophage‐like cells in muscularis externa of mouse small intestine: immunohistochemical localization of F4/80, M1–70, and la‐antigen. Cell Tissue Res. In press.
 12. Sanders, K. M., and T. K. Smith. Enteric neural regulation of slow waves in circular muscle of canine proximal colon. J. Physiol. Lond. 377: 297–313, 1986.
 13. Smith, T. K., J. B. Reed, and K. M. Sanders. Origin and propagation of electrical slow waves in circular muscle of canine proximal colon. Am. J. Physiol. 252 (Cell Physiol. 21): C215–C224, 1987.
 14. Szurszewski, J. H. Electrical basis for gastrointestinal motility. In: Physiology of the Gastrointestinal Tract (2nd ed.), edited by L. R. Johnson. New York: Raven, 1987, p. 383–422.

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Article Title: Interstitial cells of Cajal
 

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Lars Thuneberg. Interstitial cells of Cajal. Compr Physiol 2011, Supplement 16: Handbook of Physiology, The Gastrointestinal System, Motility and Circulation: 349-386. First published in print 1989. doi: 10.1002/cphy.cp060110