Ultrastructural Demonstration of ICC
ICC are characterized by such ultrastructural features as the presence of numerous mitochondria, abundant intermediate filaments, moderately developed Golgi apparatus, granular and smooth endoplasmic reticulum, close contacts with nerve varicosities and formation of gap junctions with each other and with smooth muscle cells. However, ICC show a certain range of morphological heterogeneity ranging from features similar to fibroblasts to those specific to smooth muscles cells such as caveolae, a basal lamina and subsurface cisterns, depending on their anatomical location and species.
ICC are classified into three types. On one hand, Type 1 ICC are the least like muscle cells and the most like fibroblasts, while on the other hand, Type 3 are the most similar to smooth muscle cells. Type 2 ICC have an intermediate character.
ICC associated with the myenteric plexus (ICC-MP) show some variations depending on the organ and the species in which they are found, and thus a specific set of ultrastructural features cannot be generalized. Important criteria of ICC distinguishing these cells from fibroblasts, such as the basal lamina and caveolae, are not always found in ICC-MP, though abundant mitochondria in the cytoplasm and large gap junctions are common. For example, ICC-MP of the mouse stomach show Type 3 ultrastructural features (most muscle-like features), while ICC-MP of the mouse small intestine have the least muscle-like features. In this respect, ICC-MP requires careful observations to correctly identify and interpret them.
ICC located within the circular (ICC-CM) and longitudinal (ICC-LM) muscle layers are prominent in the stomach and colon but not in the small intestine in the laboratory rodents. ICC-CM and ICC-LM of the stomach and colon have similar ultrastructural features, or Type 2 intermediate characteristics. These cells connect with neighboring smooth muscle cells via many large gap junctions and often show close contacts with nerve terminals containing many synaptic vesicles.
Ultrastructural features of ICC associated with the deep muscular plexus (ICC-DMP) do not show major differences among the species and these cells belong to Type 3 most muscle-like ICC. The most conspicuous feature of ICC-DMP is the frequent occurrence of large gap junctions that interconnect these cells with each other and also with smooth muscle cells. ICC-DMP have close contacts with nerve varicosities containing accumulations of synaptic vesicles. This means that ICC-DMP are intercalated between nerves and smooth muscle cells. Therefore, it is quite possible that ICC-DMP can act as an accessory route for neuromuscular transmission, as originally suggested by Cajal.
ICC associated with the submuscular plexus (ICC-SMP) of the colon are observed at the interface between the submucosa and the circular muscle layer. They have similar features to ICC-DMP and belong to Type 3 most muscle-like ICC. A specialized pacemaker function has been proposed in the colon, with ICC-SMP primarily responsible for generating the slow waves, and ICC-MP acting as secondary pacemaker cells.