Signal Pathways Between Nerves and Muscles Not Mediated by ICC
While an intercalated role of ICC in the neurotransmission to the smooth muscles has been demonstrated, there are morphological observations suggesting other possible forms of communication between nerves and smooth muscles.
Fibroblast-like cells (FL) were reported in the earlier studies of ICC in the tunica muscularis at different levels of the digestive tract of many species, including mouse small intestine, dog colon, and human small intestine and colon. The studies by Komuro and his group repeatedly revealed FL with small gap junctions in every tissue layer of every organ where ICC are located in the mice, rats, and guinea-pigs. It was assumed that their gap junctions act as routes for intercellular communication; conducting electrical or molecular signals for muscle contraction. Synapse-like close contacts between the FL and nerve varicosities containing many synaptic vesicles were observed in the guinea-pig small intestine.
A remarkable feature of FL is that they all show very similar ultrastructural characteristics irrespective of the tissue layer, organ, or species in which they are found. The common features of FL suggest that they may have a more fundamental role than ICC regarding mediator function in the regulation of muscle contraction.
Recent progress on the studies of fibroblast-like cells revealed that these cells are c-Kit negative, but are labeled with antibodies for platelet derived growth factor α (PDGFRα) and small conductance Ca2+-activated K+(SK3) channels. Physiological experiments using the mouse suggested that these cells mediate inhibitory responses to purines in the smooth muscles.
Further, there are morphological observations suggesting direct communication between the nerves and muscles without intercalation of any type of cells.
Those are, direct synaptic contact between the nerve varicosities and muscle cells, membrane contact between a process of the muscle cell and the axon varicosity within the myenteric ganglia, and peg-and-pocket junction between the muscle cell and the glial cell within the myenteric ganglia.