Deficiency of intramuscular ICC increases fundic muscle excitability but does not impede nitrergic innervation.
The motility of the gastrointestinal tract is generated by smooth muscle cells and is controlled to a large extent by an intrinsic neural network. A gap of approximately 200 nm usually separates nerve varicosities from smooth muscle cells, which suggests that direct innervation of the smooth muscle by synapses does not occur. Enteric nerves do make synapse-like contact with proposed regulatory cells, the interstitial cells of Cajal (ICC), which in turn may be in gap junction contact with smooth muscle cells. The role played by ICC in enteric innervation is controversial. Experimental evidence has been presented in vitro for the hypothesis that nitrergic inhibitory innervation is strongly reduced in the absence of ICC. However, in vivo data appear to dispute that. The present report provides evidence that explains the discrepancy between in vivo and in vitro data and provides evidence that inhibitory neurotransmitters can reach smooth muscle cells without hindrance when ICC are absent. The fundic musculature shows increased responses to substance P-mediated innervation and shows marked spontaneous activity, which is consistent with increased muscle excitability.
Huizinga
Jan D
JD
Intestinal Disease Research Program, Department of Medicine, McMaster University, Hamilton, ON, L8N 3Z5, Canada. huizinga@mcmaster.ca
Liu
Louis W C
LW
Fitzpatrick
Amanda
A
White
Elizabeth
E
Gill
Sandeep
S
Wang
Xuan-Yu
XY
Zarate
Natalia
N
Krebs
Lynn
L
Choi
Catherine
C
Starret
Tanya
T
Dixit
Devika
D
Ye
Jing
J
D018663:Adrenergic Agents / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D004558:Electric Stimulation; D017615:Enteric Nervous System / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005748:Gastric Fundus / Q000294:innervation / Q000502:physiology; D006145:Guanethidine / Q000494:pharmacology; D007150:Immunohistochemistry; D051379:Mice; D008854:Microscopy, Electron; D018721:Muscarinic Agonists / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000294:innervation / Q000502:physiology* / Q000648:ultrastructure; D018377:Neurotransmitter Agents / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D051381:Rats; D013270:Stomach / Q000166:cytology* / Q000502:physiology* / Q000648:ultrastructure
D018663:Adrenergic Agents; D004791:Enzyme Inhibitors; D018721:Muscarinic Agonists; D018377:Neurotransmitter Agents; D019335:Nitroarginine; D009569:Nitric Oxide; D001285:Atropine; D019001:Nitric Oxide Synthase; D006145:Guanethidine