Interstitial cells of Cajal mediate enteric inhibitory neurotransmission in the lower esophageal and pyloric sphincters

Gastroenterology. 1998 Aug;115(2):314-29. doi: 10.1016/s0016-5085(98)70198-2.


Background & aims: Previous studies have suggested that a specific class of interstitial cells of Cajal (ICC) act as mediators in nitrergic inhibitory neurotransmission. The aim of this investigation was to examine the role of intramuscular ICC (IC-IM) in neurotransmission in the murine lower esophageal (LES) and pyloric sphincters (PS).

Methods: Immunohistochemistry and electrophysiology were used to study the distribution and role of IC-IM.

Results: The LES and PS contain spindle-shaped IC-IM, which form close relationships with nitric oxide synthase-containing nerve fibers. The PS contains ICC within the myenteric plexus and c-Kit immunopositive cells along the submucosal surface of the circular muscle. IC-IM were absent in the LES and PS of c-kit (W/Wv) mutant mice. Using these mutants, we tested whether IC-IM mediate neural inputs in the LES and PS. Although the distribution of inhibitory nerves was normal in W/Wv animals, NO-dependent inhibitory neurotransmission was reduced. Hyperpolarizations to sodium nitroprusside were also attenuated in W/Wv animals.

Conclusions: The data suggest that IC-IM play an important role in NO-dependent neurotransmission in the LES and PS. IC-IM may be the effectors that transduce NO signals into hyperpolarizing responses. Loss of IC-IM may interfere with relaxations and normal motility in these sphincters.

Publication types

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

MeSH terms

  • Animals
  • Electric Stimulation
  • Electrophysiology
  • Esophagogastric Junction / cytology
  • Esophagogastric Junction / innervation*
  • Esophagogastric Junction / metabolism
  • Immunohistochemistry
  • Intestines / innervation*
  • Mice
  • Mutation / physiology
  • Nerve Fibers / physiology
  • Neural Inhibition / physiology*
  • Nitroprusside / pharmacology
  • Proto-Oncogene Proteins c-kit / metabolism
  • Pylorus / cytology
  • Pylorus / innervation*
  • Pylorus / metabolism
  • Synaptic Transmission / physiology*


  • Nitroprusside
  • Proto-Oncogene Proteins c-kit