Synaptic specializations exist between enteric motor nerves and interstitial cells of Cajal in the murine stomach

Publisher Website
Google Scholar
Abstract
Autonomic neurotransmission is thought to occur via a loose association between nerve varicosities and smooth muscle cells. In the gastrointestinal tract ultrastructural studies have demonstrated close apposition between enteric nerves and intramuscular interstitial cells of Cajal (ICC‐IM) in the stomach and colon and ICC in the deep muscular plexus (ICC‐DMP) of the small intestine. In the absence of ICC‐IM, postjunctional neural responses are compromised. Although membrane specializations between nerves and ICC‐IM have been reported, the molecular identity of these specializations has not been studied. Here we have characterized the expression and distribution of synapse‐associated proteins between nerve terminals and ICC‐IM in the murine stomach. Transcripts for the presynaptic proteins synaptotagmin, syntaxin, and SNAP‐25 were detected. Synaptotagmin and SNAP‐25‐immunopositive nerve varicosities were concentrated in varicose regions of motor nerves and were closely apposed to ICC‐IM but not smooth muscle. W/WV mice were used to examine the expression and distribution of synaptic proteins in the absence of ICC‐IM. Transcripts encoding synaptotagmin, syntaxin, and SNAP‐25 were detected in W/WV tissues. In the absence of ICC‐IM, synaptotagmin and SNAP‐25 were localized to nerve varicosities. Reverse transcriptase polymer chain reaction (RT‐PCR) and immunohistochemistry demonstrated the expression of postsynaptic density proteins PSD‐93 and PSD‐95 in the stomach and expression levels of PSD‐93 and PSD‐95 were reduced in W/WV mutants. These data support the existence of synaptic specializations between enteric nerves and ICC‐IM in gastric tissues. In the absence of ICC‐IM, components of the synaptic vesicle docking and fusion machinery is trafficked and concentrated in enteric nerve terminals. J. Comp. Neurol. 493:193–206, 2005.