, Volume 344, Issue 1, pp 17-30
Date: 22 Feb 2011

Relationship between interstitial cells of Cajal, fibroblast-like cells and inhibitory motor nerves in the internal anal sphincter

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Abstract

Interstitial cells of Cajal (ICC) have been shown to participate in nitrergic neurotransmission in various regions of the gastrointestinal (GI) tract. Recently, fibroblast-like cells, which are positive for platelet-derived growth factor receptor α (PDGFRα+), have been suggested to participate additionally in inhibitory neurotransmission in the GI tract. The distribution of ICC and PDGFRα+ cell populations and their relationship to inhibitory nerves within the mouse internal anal sphincter (IAS) are unknown. Immunohistochemical techniques and confocal microscopy were therefore used to examine the density and arrangement of ICC, PDGFRα+ cells and neuronal nitric-oxide-synthase-positive (nNOS+) nerve fibers in the IAS of wild-type (WT) and W/W v mice. Of the total tissue volume within the IAS circular muscle layer, 18% consisted in highly branched PDGFRα+ cells (PDGFRα+-IM). Other populations of PDGFRα+ cells were observed within the submucosa and along the serosal and myenteric surfaces. Spindle-shaped intramuscular ICC (ICC-IM) were present in the WT mouse IAS but were largely absent from the W/W v IAS. The ICC-IM volume (5% of tissue volume) in the WT mouse IAS was significantly smaller than that of PDGFRα+-IM. Stellate-shaped submucosal ICC (ICC-SM) were observed in the WT and W/W v IAS. Minimum surface distance analysis revealed that nNOS+ nerve fibers were closely aligned with both ICC-IM and PDGFRα+-IM. An even closer association was seen between ICC-IM and PDGFRα+-IM. Thus, a close morphological arrangement exists between inhibitory motor neurons, ICC-IM and PDGFRα+-IM suggesting that some functional interaction occurs between them contributing to inhibitory neurotransmission in the IAS.

This work was supported by grants DK078736 to K.D.K., DK057236 to S.M.W. and COBRE P20RR018751 to G.W.H. and by grant PPG DK41315. Imaging analysis was performed in a Core laboratory supported by P20RR018751.