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Type: Journal article
Title: Loss of enteric motor neurotransmission in the gastric fundus of Sl/Sld mice
Author: Spencer, E.
Horiguchi, K.
Khoyi, M.
Sanders, K.
Ward, S.
Citation: The Journal of Physiology, 2002; 543(3):871-887
Publisher: Blackwell Publishing Ltd
Issue Date: 2002
ISSN: 0022-3751
Statement of
Elizabeth A. H. Beckett, Kazuhide Horiguchi, Mohammad Khoyi, Kenton M. Sanders and Sean M. Ward
Abstract: Studies of W/WV mice, which lack intramuscular interstitial cells of Cajal (IC-IM), have suggested that IC-IM act as mediators of enteric motor neurotransmission in the gastrointestinal tract. We have studied Sl/Sld mice, which lack the ability to make membrane-bound stem cell factor, to determine the consequences of inappropriate stem cell factor expression on IC-IM populations and on enteric motor neurotransmission. IC-IM were found within the circular and longitudinal muscles of the gastric fundus of wild-type mice. IC-IM were intimately associated with motor nerve terminals and nerve varicosities formed synaptic structures with these cells. IC-IM were also connected with neighbouring smooth muscle cells via gap junctions. Immunohistochemistry and electron microscopy showed that IC-IM were absent from fundus muscles of Sl/Sld mice, but the density of excitatory and inhibitory nerves was not significantly different than in wild-type muscles. Loss of IC-IM was associated with decreased membrane noise (unitary potentials) and significant reductions in post-junctional excitatory and inhibitory enteric nerve responses. Reductions in neural responses were not due to defects in smooth muscle cells as responses to exogenous ACh and K+-induced depolarization were normal in Sl/Sld mice. Responses to neurally released ACh were revealed in Sl/Sld mice by inhibiting ACh breakdown with the acetylcholinesterase inhibitor neostigmine. Inhibitory nerve stimulation elicited inhibitory junction potentials (IJPs) and relaxations in wild-type mice. IJPs were reduced in amplitude and relaxation responses were absent in Sl/Sld mice. These observations suggest that membrane-bound stem cell factor is essential for development of IC-IM and that the close, synaptic-like relationship between nerve terminals and IC-IM may be the primary site of innervation by enteric motor neurons in gastric muscles.
Keywords: Muscle, Smooth
Gastric Fundus
Motor Neurons
Enteric Nervous System
Mice, Mutant Strains
Cholinesterase Inhibitors
Vasodilator Agents
Microscopy, Electron
Electric Stimulation
Synaptic Transmission
Excitatory Postsynaptic Potentials
Muscle Tonus
Description: Copyright © 2002 The Physiological Society
DOI: 10.1113/jphysiol.2002.021915
Published version:
Appears in Collections:Aurora harvest
Molecular and Biomedical Science publications

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