Abstract

Intramuscular interstitial cells of Cajal (ICC-IM) are closely associated with enteric motor nerve terminals and electrically coupled to smooth muscle cells within the gastric musculature. Previous studies investigating the role of ICC-IM in motor neurotransmission have used indiscriminate electric field stimulation of neural elements within the gastric wall. To determine the role of ICC-IM in transduction of vagally-mediated motor input to gastric muscles electrical and mechanical responses to selective electrical vagal stimulation (EVS) were recorded from gastric fundus and antral regions of wild type and W/WV mice, which lack most ICC-IM. EVS evoked inhibitory junction potentials (IJPs) in wild type muscles that were attenuated or abolished by L-NNA. IJPs were rarely evoked in W/WV muscles by EVS, and not affected by L-NNA. EVS evoked relaxation of wild type stomachs, but the predominant response of W/WV stomachs was contraction. EVS applied after pre-contraction with bethanechol caused relaxation of wild type gastric tissues and these were inhibited by the nitric oxide synthase inhibitor L-NNA. Relaxation responses were of smaller amplitude in W/WV muscles and L-NNA did not attenuate relaxation responses in W/WV fundus muscles. These data suggest an important role for ICC-IM in vagally-mediated nitrergic relaxation in the proximal and distal stomach.

Highlights

  • Intramuscular interstitial cells of Cajal (ICC-IM) are closely associated with enteric motor nerve terminals and electrically coupled to smooth muscle cells within the gastric musculature

  • Previous studies have suggested a role for ICC-IM in both cholinergic excitatory and nitrergic inhibitory motor neurotransmission in the gastric fundus and antrum[7,8,9,10,11], suggesting that ICC-IM are innervated, provide mechanisms of transduction of neural signals to the gastric musculature, and play a role in the gastric accommodation reflex

  • Short trains of electric vagal stimulation (EVS; 1–20 Hz applied for 0.5–1 s) elicited inhibitory junction potentials (IJPs) in the fundus and antral regions of wild type stomachs

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Summary

Introduction

Intramuscular interstitial cells of Cajal (ICC-IM) are closely associated with enteric motor nerve terminals and electrically coupled to smooth muscle cells within the gastric musculature. To determine the role of ICC-IM in transduction of vagally-mediated motor input to gastric muscles electrical and mechanical responses to selective electrical vagal stimulation (EVS) were recorded from gastric fundus and antral regions of wild type and W/WV mice, which lack most ICC-IM. Relaxation responses were of smaller amplitude in W/WV muscles and L-NNA did not attenuate relaxation responses in W/WV fundus muscles These data suggest an important role for ICC-IM in vagally-mediated nitrergic relaxation in the proximal and distal stomach. Previous studies have suggested a role for ICC-IM in both cholinergic excitatory and nitrergic inhibitory motor neurotransmission in the gastric fundus and antrum[7,8,9,10,11], suggesting that ICC-IM are innervated, provide mechanisms of transduction of neural signals to the gastric musculature, and play a role in the gastric accommodation reflex. The importance of ICC-IM in nitrergic inhibitory responses that are initiated through vagal motor inputs to the stomach and are fundamental to gastric accommodation

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