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 cir-cular layer of the mouse colon where a co-transmission of purines acting on P2Y1receptors and NO has been previously described. However, the corresponding mech-anisms 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 proxi-mal, 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 heterolo-gous 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.