The asymmetric innervation of the circular and longitudinal muscle of the mouse colon differently modulates myogenic slow phasic contractions

Abstract

Background Neuromuscular transmission has been extensively studied in the circular layer of the mouse colon where a co‐transmission of purines acting on P2Y1 receptors and NO has been previously described. However, the corresponding mechanisms in the longitudinal layer are less known. Methods Electrophysiological and myography techniques were used to evaluate spontaneous phasic contractions (SPC) and neural‐mediated responses in the proximal, mid, and distal colon devoid of CD1 mice. Immunohistochemistry against c‐kit and PDGFRα was performed in each colonic segment. Key Results SPC were recorded in both muscle layers at a similar frequency being about four contractions per minute (c.p.m.) in the proximal and distal colon compared to the mid colon (2 c.p.m.). In non‐adrenergic, non‐cholinergic conditions, L‐NNA (1 mmol/L) increased contractility in the circular but not in the longitudinal layer. In the longitudinal muscle, both electrophysiological and mechanical neural‐mediated inhibitory responses were L‐NNA and ODQ (10 µmol/L) sensitive. NaNP (1 µmol/L) caused cessation of SPC and the response was blocked by ODQ. Neither ADPßS (10 µmol/L) nor CYPPA (10 µmol/L), which both targeted the purinergic pathway, altered longitudinal contractions. PDGFRα + cells were located in both muscle layers and were more numerous compared with cKit + cells, which both formed a heterologous cellular network. A decreasing gradient of the PDGFRα labeling was observed along the colon. Conclusion An inhibitory neural tone was absent in the longitudinal layer and neuronal inhibitory responses were mainly nitrergic. Despite the presence of PDGFRα + cells, purinergic responses were absent. Post‐junctional pathways located in different cell types might be responsible for neurotransmitter transduction.

The Telocytes: Ten Years after Their Introduction in the Scientific Literature. An Update on Their Morphology, Distribution, and Potential Roles in the Gut

“…In the gut muscle coat, the TC network runs parallel or even intercalates with that formed by the ICCs [ 15 , 16 , 17 , 18 ] so the possibility that TCs and ICCs could be the same cell type was initially considered. However, by using IHC, TEM and immune-TEM techniques, the unique identity of the TCs has been clearly proven [ 16 , 17 ].…”

“…However, by using IHC, TEM and immune-TEM techniques, the unique identity of the TCs has been clearly proven [ 16 , 17 ]. These studies showed, by IHC and immune-TEM, that TCs express CD34 [ 16 ] and, by IHC, PDGFRα and that they were c-Kit negative [ 17 , 18 , 19 , 20 ]; conversely, ICCs that were c-Kit positive expressed none of these two markers (for ICC ultrastructural features, see the related insert). At the myenteric plexus and in the thickness of the muscle layers, TCs and ICCs form three-dimensional (3-D) networks, whereas, at the border between the circular muscle layer and the submucosa, the networks are bi-dimensional (2-D).…”

“…At the myenteric plexus and in the thickness of the muscle layers, TCs and ICCs form three-dimensional (3-D) networks, whereas, at the border between the circular muscle layer and the submucosa, the networks are bi-dimensional (2-D). However, the TC network faces the submucosal border while that of ICCs faces the muscular one [ 15 , 16 , 17 , 18 , 19 ].…”

“…Interestingly, although synaptic-like contacts between nerve varicosities and TCs were not observed under the TEM, it has been demonstrated that TCs express purine receptors P2Y1 and apamin-sensitive SK3 channels and respond to agonists and antagonists to these receptors [ 18 , 19 , 41 , 42 , 43 ]. Furthermore, the TCs/PDGFRα-positive cells selectively expressed the SK3 channel among all the ICs present in the gut interstitium [ 44 ] and significant changes in the functionality of these receptors have been associated with GI diseases [ 45 , 46 , 47 ].…”

Telocytes: An Emerging Component of Stem Cell Niche Microenvironment

“…118 This finding led to propose TCs as mediators of the macrophage actions on smooth muscle cells. 118 Finally, as it has been reported that the TCs located in the tunica muscularis of the gut express both purine receptors P2Y1 and apamin-sensitive SK3 channels and respond to agonists and antagonists to these receptors, 107,[119][120][121][122] an additional role raised for gastrointestinal TCs is that of representing targets of neural signals. Interestingly, changes in the functionality of such receptors have been associated with different gastrointestinal diseases.…”