Vagal intramuscular array afferents form complexes with interstitial cells of Cajal in gastrointestinal smooth muscle: analogues of muscle spindle organs?

Abstract

Intramuscular arrays (IMAs), vagal mechanoreceptors that innervate gastrointestinal smooth muscle, have not been completely described structurally or functionally. To delineate more fully the architecture of IMAs and to consider the structure-function implications of the observations, the present experiment examined the organization of the IMA terminal arbors and the accessory tissue elements of those arbors. IMA terminal fields, labeled by injection of biotinylated dextran into the nodose ganglia, were examined in whole mounts of rat gastric smooth muscle double-labeled with immunohistochemistry for interstitial cells of Cajal (ICCs; c-Kit) and/or inputs of different neuronal efferent transmitter (markers: TH, VChAT, and NOS) or afferent neuropeptidergic (CGRP) phenotypes. IMAs make extensive varicose and lamellar contacts with ICCs. In addition, axons of the multiple efferent and afferent phenotypes examined converge and articulate with IMA terminal arbors innervating ICCs. This architecture is consistent with the hypothesis that IMAs, or the multiply innervated IMA-ICC complexes they form, can function as stretch receptors. The tissue organization is also consonant with the proposal that those units can operate as functional analogues of muscle spindle organs. For electrophysiological assessments of IMA functions, experiments will need protocols that preserve both the complex architecture and the dynamic operations of IMA-ICC complexes.

Extrinsic primary afferent signalling in the gut

“…[49][50][51] Morphologically, several types of vagal mucosal endings have been distinguished. In the small intestine there are endings that project along the length of the villi, ramifying beneath the epithelial layer 52 . Another type encircles the Crypts of Lieberkuhn and do not penetrate into the villi.…”

“…Another type encircles the Crypts of Lieberkuhn and do not penetrate into the villi. 52 Vagal mucosal afferents are often potently activated by mediators released from the extensive populations of enteroendocrine cells found in the mucosa. There are 10-20 classes of enteroendocrine cells, each of which releases a subset of about 20 mediators, often in response to nutrients.…”

“…70 They are densest in the fundus and in the sphincteric regions of the stomach 71 where they run close to intramuscular interstitital cells of Cajal (ICC). 52 This has led to the speculation that intramuscular arrays, intramuscular ICC, and possibly efferent nerve fibres, might form functional complexes, perhaps analogous to striated muscle spindles. To date, no electrophysiological activity has been recorded that can confidently be attributed to vagal intramuscular arrays.…”

Interstitial cells of Cajal and telocytes in the gut: twins, related or simply neighbor cells?

“…Another function attributed to some ICC populations is that of being part of the 'stretch receptor'. In particular, in the small intestine this role would be played by the ICC-DMP (11,12,20,21), in the stomach, by the ICC-IM (22).…”

The Significance of Interstitial Cells in Neurogastroenterology

“…ICC-IM also act as mechanosensitive regulators of pacemaker activity 47,48 and play a role in the guidance of vagal afferent nerves that form intramuscular arrays in the stomach. [49][50][51] It should also be noted that ICC-IM may be capable of generating pacemaker activity in some regions. For example in the corpus of the stomach, primary pacemaker activity was attributed to ICC-IM.…”