Loss of enteric motor neurotransmission in the gastric fundus of Sl/Sl(d) mice.
Studies of W/W(V) 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/Sl(d) 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/Sl(d) 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/Sl(d) mice. Responses to neurally released ACh were revealed in Sl/Sl(d) 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/Sl(d) 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.
Beckett
Elizabeth A H
EA
Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557, USA.
Horiguchi
Kazuhide
K
Khoyi
Mohammad
M
Sanders
Kenton M
KM
Ward
Sean M
SM
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D016477:Artifacts; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D004558:Electric Stimulation; D017615:Enteric Nervous System / Q000166:cytology / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005748:Gastric Fundus / Q000294:innervation*; D051379:Mice; D008817:Mice, Mutant Strains / Q000502:physiology*; D008854:Microscopy, Electron; D009046:Motor Neurons / Q000502:physiology* / Q000648:ultrastructure; D009129:Muscle Tonus / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000294:innervation; D009388:Neostigmine / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D009435:Synaptic Transmission / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D002800:Cholinesterase Inhibitors; D014665:Vasodilator Agents; D009599:Nitroprusside; D009388:Neostigmine; D000109:Acetylcholine