Colonic elongation inhibits pellet propulsion and migrating motor complexes in the murine large bowel

Abstract

The colonic migrating motor complex (CMMC) is a rhythmically occurring neurally mediated motor pattern. Although the CMMC spontaneously propagates along an empty colon it is responsible for faecal pellet propulsion in the murine large bowel. Unlike the peristaltic reflex, the CMMC is an 'all or none' event that appears to be dependent upon Dogiel Type II/AH neurons for its regenerative slow propagation down the colon. A reduction in the amplitude of CMMCs or an elongated colon have both been thought to underlie slow transit constipation, although whether these phenomena are related has not been considered. In this study we examined the mechanisms by which colonic elongation might affect the CMMC using video imaging of the colon, tension and electrophysiological recordings from the muscle and Ca 2+ imaging of myenteric neurons. As faecal pellets were expelled from the murine colon, it shortened by up to ∼29%. Elongation of the colon resulted in a linear reduction in the velocity of a faecal pellet and the amplitude of spontaneous CMMCs. Elongation of the oral end of a colonic segment reduced the amplitude of CMMCs, whereas elongation of the anal end of the colon evoked a premature CMMC, and caused the majority of CMMCs to propagate in an anal to oral direction. Dogiel Type II/AH sensory neurons and most other myenteric neurons responded to oral elongation with reduced amplitude and frequency of spontaneous Ca 2+ transients, whereas anal elongation increased their amplitude and frequency in most neurons. The inhibitory effects of colonic elongation were reduced by blocking nitric oxide (NO) production with l-NA (100 μm) and soluble guanylate cyclase with 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 10 μm); whereas, l-arginine (1-2 mm) enhanced the inhibitory effects of colonic elongation. In conclusion, polarized neural reflexes can be triggered by longitudinal stretch. The dominant effect of elongation is to reduce CMMCs primarily by inhibiting Dogiel Type II/AH neurons, thus facilitating colonic accommodation and slow transit.

Optical Tools to Investigate Cellular Activity in the Intestinal Wall

“…However, as opposed to many live imaging studies focusing on other parts of the nervous system, only few reports have examined activity patterns of neuronal circuits underlying integrated ENS output such as for example the colonic migrating motor complex. [103][104][105] Nevertheless, imaging of cultured enteric neurons and ex vivo tissue preparations have clarified important physiological characteristics of enteric neurons such as their mechanosensitivity, and thereby challenged the classic ideas on sensory transmission and reflex activity in the ENS. 106,107 The majority of studies in the gut have used classic live imaging techniques and synthetic indicator dyes, to monitor activity of the various cell types that govern GI motility.…”

Colonic Migrating Motor Complexes, High Amplitude Propagating Contractions, Neural Reflexes and the Importance of Neuronal and Mucosal Serotonin

“…2). Although these propagating contractions have been given a variety of names such as CMMCs, giant migrating contractions, giant contractions, myoelectric complexes, migrating spike bursts, peristaltic contractions, HAPCs and propagating pressure sequences, 8,[57][58][59][60][61][62][63][64][65][66][67][68][69][70][71] they are probably generated by similar mechanisms ( Fig. 2 and 3).…”

“…These particular interneurons release nitric oxide (NO) to depress myenteric neurons underlying the CMMC and peristalsis. 69,76,77 Blocking NO synthesis in healthy humans increases the number of propagating contractions. 68 Furthermore, flushing the human colon increases the number of HAPCs.…”

“…63,72 Their rarity may be due to myenteric neurons being normally inhibited by sympathetic nervous activ- ity 63,[73][74][75] or the intrinsic occult inhibitory neural reflex. 69,76,77 The occult inhibitory reflex is triggered by colonic elongation caused by the accumulation of fecal matter. 69,76 Colonic elongation activates mainly long descending mechanosensitive nNOS positive sensory interneurons that are triggered by longitudinal stretch.…”

“…69,76,77 The occult inhibitory reflex is triggered by colonic elongation caused by the accumulation of fecal matter. 69,76 Colonic elongation activates mainly long descending mechanosensitive nNOS positive sensory interneurons that are triggered by longitudinal stretch. These particular interneurons release nitric oxide (NO) to depress myenteric neurons underlying the CMMC and peristalsis.…”