Responses to Enteric Motor Neurons in the Gastric Fundus of Mice With Reduced Intramuscular Interstitial Cells of Cajal

Abstract

Background/AimsInterstitial cells of Cajal (ICC) play important functions in motor activity of the gastrointestinal tract. The role of ICC as pacemakers is well established, however their participation in neurotransmission is controversial. Studies using mutant animals that lack ICC have yielded variable conclusions on their importance in enteric motor responses. The purpose of this study was to:(1) clarify the role of intramuscular ICC (ICC-IM) in gastric motor-neurotransmission and (2) ConclusionsThis study demonstrates that ICC-IM mediate nitrergic inhibitory neurotransmission in the fundus and provides evidence of plasticity changes in neuronal responses that may explain discrepancies in previous functional studies which utilized mutant animals to examine the role of ICC-IM in gastric enteric motor responses.

Change in the Interstitial Cells of Cajal and nNOS Positive Neuronal Cells with Aging in the Stomach of F344 Rats

“…Second, we used corpus (proximal glandular stomach) area of rat stomach for the quantitative (morphological) or molecular experiment instead of forestomach. Although many previous studies [22, 38, 44, 59] reported about the experiment of gastric relaxation in murine, there was no definite mention about the precise region of fundus in the murine stomach. The stomach of the rat is divided into the forestomach (pars proventricularis) and glandular stomach (corpus or pars glandularis), which is different from human.…”

“…Recently, Sanders et al . revealed that the inhibitory responses were absent or reduced when ICC-IM were partially or completely lost, providing evidence for the role of ICC-IM in mediating inhibitory neurotransmission in the gastric fundus of W/W V mice [22]. Furthermore, decrease or loss of ICC in the human gut was frequently observed in the diabetic gastroenteropathy [23] or slow transit constipation [24, 25].…”

Spontaneous Ca2+ transients in interstitial cells of Cajal located within the deep muscular plexus of the murine small intestine

“…; Sanders et al . a ). ICC‐DMP also appear to contribute to neurokinin responses initiated by peptidergic motor neurons because they express NK1 receptors and internalize these receptors during nerve stimulation (Iino et al .…”

Inhibitory responses mediated by vagal nerve stimulation are diminished in stomachs of mice with reduced intramuscular interstitial cells of Cajal

“…In a re-evaluation of this question we found that the lesion in ICC-IM varies to some extent in different animals. When ICC-IM were greatly reduced, nitrergic responses were greatly reduced, but when clusters of ICC-IM remained, nitrergic responses were observed12. A recent study using cell-specific inducible Cre recombinase (iCre) to knock down soluble guanylate cyclase (sGC) found that nitrergic responses were affected only to a minor extent when the lesion in sGC was directed at ICC and only partially decreased when sGC was knocked down in smooth muscle cells19.…”