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

Neurogastroenterol Motil. 2020 Apr;32(4):e13778. doi: 10.1111/nmo.13778. Epub 2019 Dec 17.

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.

Keywords: PDGFRα + cells; immunohistochemistry; interstitial cells of Cajal; longitudinal colon; relaxation; smooth muscle; telocytes.

MeSH terms

  • Animals
  • Colon / innervation*
  • Colon / physiology*
  • Mice
  • Muscle Contraction / physiology*
  • Muscle, Smooth / innervation*
  • Muscle, Smooth / physiology*
  • Synaptic Transmission / physiology*