Interstitial cells of Cajal mediate enteric inhibitory neurotransmission in the lower esophageal and pyloric sphincters.
OBJECTIVE
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.
Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada, USA.
S M
SM
Ward
G
G
Morris
L
L
Reese
X Y
XY
Wang
K M
KM
Sanders
D000818:Animals; D004558:Electric Stimulation; D004594:Electrophysiology; D004943:Esophagogastric Junction / Q000166:cytology / Q000294:innervation* / Q000378:metabolism; D007150:Immunohistochemistry; D007422:Intestines / Q000294:innervation*; D051379:Mice; D009154:Mutation / Q000502:physiology; D009412:Nerve Fibers / Q000502:physiology; D009433:Neural Inhibition / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D011708:Pylorus / Q000166:cytology / Q000294:innervation* / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology*
D009599:Nitroprusside; D019009:Proto-Oncogene Proteins c-kit