Submitted on March 16, 2007
Accepted on December 6, 2007
Deficiency of intramuscular ICC increases fundic muscle excitability but does not impede nitrergic innervation
Jan D. Huizinga1*, Louis W.C. Liu1, Amanda Fitzpatrick1, Elizabeth Jessie White1, Sandeep Gill1, Xuan-Yu Wang2, Natalia Zarate1, Lynn Krebs1, Catherine Choi1, Tanya Starret1, Devika Dixit1, and Jing Ye1
1 Intestinal Disease Research Program, McMaster University, Hamilton, Canada
2 Intestinal Disease Research Program, Mc Master University, Hamilton, Canada
* To whom correspondence should be addressed. E-mail: huizinga{at}mcmaster.ca.
The motility of the gastrointestinal tract is generated by smooth muscle cells and controlled to a large extent by an intrinsic neural network. A gap of ~ 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.
