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Abstract
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).
Immunohistochemistry and electrophysiology were used to study the distribution and
role of IC-IM.
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.
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.