Responses to enteric motor neurons in the gastric fundus of mice with reduced intramuscular interstitial cells of cajal

Interstitial cells of Cajal (ICC) play important functions in motor activity of the gastrointestinal tract. The role of ICC as pace-makers 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) evaluate remodeling of enteric mo-tor responses in W/W(V) mice.

Interstitial cells of Cajal (ICC) play important functions in motor activity of the gastrointestinal tract. The role of ICC as pace-makers 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) evaluate remodeling of enteric mo-tor responses in W/W(V) mice.

This study demonstrates that ICC-IM mediate nitrergic inhibitory neurotransmission in the fundus and provides evidence of plas-ticity 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.

Kit immunohistochemistry and post-junctional contractile responses were performed on fundus muscles from wild-type and W/W(V) mice and quantitative polymerase chain reaction (qPCR) was used to evaluate differences in muscarinic and neurokinin receptor expression.

Although ICC-IM were greatly reduced in comparison with wild-type mice, we found that ICC-IM persisted in the fundus of many W/W(V) animals. ICC-IM were not observed in W/W(V) group 1 (46%) but were observed in W/W(V) group 2 (40%). Evoked neural responses consisted of excitatory and inhibitory components. The inhibitory component (nitrergic) was absent in W/W(V) group 1 and reduced in W/W(V) group 2. Enhanced excitatory responses (cholinergic) were observed in both W/W(V) groups and qPCR re-vealed that muscarinic-M3 receptor expression was significantly augmented in the W/W(V) fundus compared to wild-type controls. Conclusions: This study demonstrates that ICC-IM mediate nitrergic inhibitory neurotransmission in the fundus and provides evidence of plas-ticity 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.