Interstitial cells of Cajal and neuromuscular transmission in the rat lower oesophageal sphincter

The distribution of interstitial cells of Cajal(ICC) and neurotransmission were investigated inlower oesophageal sphincter (LES) circular musclestrips from Sprague–Dawley (SD) rats, Ws/Ws mutantrats and their wild-type (+/+) siblings. Intramuscularc-Kit-positive cells, confirmed to be ICC-IM by elec-tron microscopy, were observed throughout bothmuscle layers from SD and +/+ rats. In contrast, c-Kit-positive, ultrastructurally typical ICC-IM were absentin Ws/Ws. LES strips from Ws/Ws rats showed in-creased spontaneous contractile activity. Strips fromSD and +/+ rats, responded to electrical neuronal sti-mulation with a relaxation that was in part L-NNAand in part apamin sensitive, followed by a contrac-tion which was decreased by atropine. In Ws/Ws rats,similar to +/+ rats, neurally mediated relaxation wasL-NNA and apamin sensitive and the contraction wasdecreased by atropine. We conclude that in the ratLES, relaxation is mediated by NO and an apamin-sensitive mediator, and contraction primarily byacetylcholine. Despite the absence of c-Kit-positiveICC, nerve–muscle interaction can be accomplishedlikely by diffusion of neurotransmitters to the smoothmuscle cells. The lack of c-Kit-positive ICC is relatedto an increase in the basal tone and spontaneouscontractile activity. The presence of fibroblast-likeICC in Ws/Ws rats might represent immature ICCwhose possible functions need further investigation.Keywords apamin, c-Kit, interstitial cells of Cajal,lower oesophageal sphincter, nitric oxide, Ws/Ws rat.