Interstitial cells of Cajal: Primary targets of enteric motor innervation

For many years morphologists have noted the close relationship between inte rstitial cells of Cajal (ICC) and nerve fibers within the tunica muscularis of gastrointestinal (GI) organs. These observations led to speculations ab out a role for ICC in mediating neural inputs to the GI tract. Immunohistoc hemical and functional studies demonstrated the presence of receptors for t he neurotransmitters utilized by enteric motor neurons, and changes in seco nd messengers in ICC after field stimulation of intrinsic enteric neurons s howed that ICC were functionally innervated in GI muscles. Recent double la beling experiments have shown that both excitatory and inhibitory enteric m otor neurons are closely associated with ICC in the deep muscular plexus (I C-DMP) of the small intestine and intramuscular ICC (IC-IM) of the proximal and distal GI tract. Enteric motor neurons form synaptic-like structures w ith IC-IM and IC-DMP, Far fewer close contacts are found between enteric mo tor neurons and smooth muscle cells. Experiments on W/W-V mutants that lack IC-IM in the stomach, lower esophageal sphincter, and pylorus have shown t hat these ICC are critical components of the neuromuscular junction. Cholin ergic excitatory and nitrergic inhibitory neurotransmission are severely de creased in tissues lacking IC-IM, yet there is no loss of cholinergic or ni trergic neurons in W/W-V mutants. These data suggest that either the post-j unctional mechanisms responsible for receiving and transducing neurotransmi tter signals are specifically expressed by ICC, or that the large extracell ular spaces typically between nerve terminals and smooth muscle cells may n ot allow effective concentrations of neurotransmitters to reach receptors e xpressed by smooth muscle cells. These findings indicate an important role for certain classes of ICC in enteric neurotransmission and predict that lo ss of ICC in human motor disturbances may significantly compromise neural r egulation of GI motility. Anat Rec 262:125-135, 2001. (C) 2001 Wiley-Liss, Inc.