Relationship between interstitial cells of Cajal and enteric motor neurons in the murine proximal colon

Cell Tissue Res. 2000 Dec;302(3):331-42. doi: 10.1007/s004410000272.


Interstitial cells of Cajal (ICC) are interposed between enteric neurons and smooth muscle cells in gastrointestinal (GI) muscles. The specific relationships between these cells in the murine proximal colon were studied with conventional and immunoelectron microscopy and immunohistochemistry. Intramuscular interstitial cells (IC-IM) formed discrete networks within the circular muscle layer of the murine proximal colon. Nerve trunks ran in close association with IC-IM and individual nerve trunks came into close contact with multiple IC-IM. Conventional electron microscopy revealed very close (< or = 20 nm) associations between nerve fibers and IC-IM. Processes of IC-IM also formed close contacts with neighboring smooth muscle cells. At the points of close association between neurons and IC-IM, areas of membrane densification in both pre- and postjunctional cells were present, suggesting specialized contacts or synaptic-like structures. Similar points of contact between neurons and smooth muscle cells were extremely rare. Immunoelectron microscopy demonstrated that IC-IM formed close associations with neurons containing nitric oxide synthase-like immunoreactivity (NOS-LI) or vesicular acetylcholine transporter-like immunoreactivity (vAChT-LI), suggesting innervation by both inhibitory and excitatory motor neurons. IC-IM were also labeled with anti-NOS antibodies. These observations suggest that IC-IM are an integral part of the neuromuscular junction in the colon. These cells may be the primary site of innervation, and neural regulation of the musculature may occur via IC-IM.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Carrier Proteins / immunology
  • Carrier Proteins / metabolism
  • Colon / cytology*
  • Colon / innervation*
  • Colon / metabolism
  • Enteric Nervous System / cytology
  • Enteric Nervous System / metabolism
  • Enteric Nervous System / ultrastructure*
  • Immunohistochemistry
  • Male
  • Membrane Transport Proteins*
  • Mice
  • Mice, Inbred BALB C
  • Microscopy, Electron
  • Microscopy, Immunoelectron
  • Motor Neurons / metabolism
  • Motor Neurons / ultrastructure*
  • Muscle, Smooth / cytology*
  • Muscle, Smooth / innervation
  • Muscle, Smooth / ultrastructure
  • Nitric Oxide Synthase / immunology
  • Nitric Oxide Synthase / metabolism
  • Stem Cell Factor / immunology
  • Stem Cell Factor / metabolism
  • Thiolester Hydrolases / immunology
  • Thiolester Hydrolases / metabolism
  • Ubiquitin Thiolesterase
  • Vesicular Acetylcholine Transport Proteins
  • Vesicular Transport Proteins*


  • Carrier Proteins
  • Membrane Transport Proteins
  • Slc18a3 protein, mouse
  • Stem Cell Factor
  • Vesicular Acetylcholine Transport Proteins
  • Vesicular Transport Proteins
  • Nitric Oxide Synthase
  • Thiolester Hydrolases
  • Ubiquitin Thiolesterase