The ultrastructure of the muscle coat of human gastro-oesophageal junction, with special reference to “interstitial cells of Cajal”†

Abstract

The muscle coat of the human lower oesophageal sphincter and stomach was studied 5 cm above and 4 cm below the gastro-oesophageal junction. Four subjects were operated on for motility disorders of the esophagus, two for a hypertensive lower oesophageal sphincter and two for an epiphrenic diverticulum; six subjects were operated on for oesophageal or gastric carcinomas. Specimens were fixed in phosphate-buffered OsO4, embedded in Epon, contrasted with uranyl acetate and lead citrate and observed under a Siemens Elmiskop Ia electron microscope. Both the oesophageal and gastric muscle cells, which showed features typical of this cell type, were innervated by multiple varicosities that were rich in synaptic vesicles; these varicosities were generally rarely encountered at distances less than 1000 Å from muscle cells. Only a very few, close neuromuscular junctions were detected. Special cells, which correspond to the “interstitial cells of Cajal” as reported by other authors, were discerned at the periphery of muscle cell bundles. These cells were characterized by an elongated cell body with many thin branches and an oval, sometimes indented nucleus. Some pinocytotic vesicles were located at the cell periphery. These cells were surrounded by a discontinuous basal lamina and were seen in close contact with each other and with muscle cells; the close contact areas were often very wide. The cytoplasm contained variable amounts of mitochondria, a well-developed smooth endoplasmic reticulum and a Golgi complex. As a characteristic feature, bundles of thin filaments were located at the cell periphery and were attached to electron-dense areas of the cell membrane. Morphologically, these filaments resembled myofilaments; they were present in variable amounts and were sometimes very numerous. The observation that the cytoplasmic organelles and filaments varied in number, is probably related to the different functional properties of these cells. Interstitial cells were richly innervated by varicose nerve fibers that were densely packed with synaptic vesicles; many close junctions to nerve endings were also detected. These morphological data lead us to assume that the interstitial cells demonstrated by the electron microscope do not correspond to the cells initially identified by Cajal and cannot even be considered connective tissue cells. We propose that they are specialized smooth muscle cells that are involved in generating spontaneous, myogenic electrical activity in the gastrointestinal tract.

Telocytes express PDGFRα in the human gastrointestinal tract

“…To date, three different interstitial cell types have been identified in the gastrointestinal (GI) tract, each forming networks within the muscle coat: The interstitial cells of Cajal (ICC) that are positive for c‐kit and negative for CD34 and platelet‐derived growth factor receptor α (PDGFRα) . These cells are considered the pacemaker cells and the mediators of neurotransmission in the GI tract . The TC that are CD34‐positive and c‐kit‐negative . Several roles have been proposed for these cells.…”

“…(i) The interstitial cells of Cajal (ICC) that are positive for c-kit and negative for CD34 and platelet-derived growth factor receptor a (PDGFRa) [2,[10][11][12][13][14][15][16][17]. These cells are considered the pacemaker cells and the mediators of neurotransmission in the GI tract [10,12,17,18]. (ii) The TC that are CD34-positive and c-kit-negative [2].…”

Interstitial cells of Cajal, from structure to function

“…a historical paper originally written in Italian and now translated by Faussone Pellegrini et al (2013). …”

“…The first paper that provided the hypothesis that ICC were pacemaker cells based on this new technique was published in an Italian journal by Professor Faussone-Pellegrini at the University of Florence, Italy, where she described ICC observed in esophageal and gastric specimen from patients not suffering from motility pathologies (Faussone Pellegrini et al, 1977). A translation of this paper in English has now appeared in Frontiers in Autonomic Neuroscience (Faussone Pellegrini et al, 2013). Faussone-Pellegrini graduated from the University of Florence in 1963 at the age of 23 and was offered a position in the Histology and Embryology Department to instruct the members of the department in the use of the new transmission electron microscope.…”

“…Faussone-Pellegrini writes: “The low degree of differentiation of interstitial cells as contractile elements might be linked to self-excitation, as in myocardium (Viragh and Challice, 1973), where the specific tissue devoted to generation and conduction of impulses is made up of cells that are less well differentiated for contraction than common myocardiocytes” (Faussone Pellegrini et al, 2013). …”