INTERSTITIAL-CELLS OF CAJAL MEDIATE ENTERIC INHIBITORY NEUROTRANSMISSION IN THE LOWER ESOPHAGEAL AND PYLORIC SPHINCTERS

Background & Aims: Previous studies have suggested that a specific cla ss of interstitial cells of Cajal (ICC) act as mediators in nitrergic inhibitory neurotransmission. The aim of this investigation was to exa mine the role of intramuscular ICC (IC-IM) in neurotransmission in the murine lower esophageal (LES) and pyloric sphincters (PS). Methods: I mmunohistochemistry and electrophysiology were used to study the distr ibution and role of IC-IM. Results: The LES and PS contain spindle-sha ped IC-IM, which form close relationships with nitric oxide synthase-c ontaining nerve fibers. The PS contains ICC within the myenteric plexu s and c-Kit immunopositive cells along the submucosal surface of the c ircular muscle. IC-IM were absent in the LES and PS of c-hit (W/W-V) m utant mice. Using these mutants, we tested whether IC-IM mediate neura l inputs in the LES and PS. Although the distribution of inhibitory ne rves was normal in W/W-V animals, NO-dependent inhibitory neurotransmi ssion was reduced. Hyperpolarizations to sodium nitroprusside were als o attenuated in W/W-V animals. Conclusions: The data suggest that IC-I M play an important role in NO-dependent neurotransmission in the LES and PS. IC-IM may be the effecters that transduce NO signals into hype rpolarizing responses. Loss of IC-IM may interfere with relaxations an d normal motility in these sphincters.