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

Background Neuromuscular transmission has been extensively studied in the circular layer of the mouse colon where a co-transmission of purines acting on P2Y(1) 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 PDGFR alpha 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 mu mol/L) sensitive. NaNP (1 mu mol/L) caused cessation of SPC and the response was blocked by ODQ. Neither ADP ss S (10 mu mol/L) nor CYPPA (10 mu mol/L), which both targeted the purinergic pathway, altered longitudinal contractions. PDGFR alpha + 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 PDGFR alpha 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 PDGFR alpha + cells, purinergic responses were absent. Post-junctional pathways located in different cell types might be responsible for neurotransmitter transduction.