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

Dante J. Heredia, Eamonn J Dickson, Peter O. Bayguinov, Grant W. Hennig, Terence K. Smith

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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 themurine large bowel. Unlike the peristaltic reflex, the CMMCis an 'all or none' event that appears to be dependent uponDogielType II/AH neurons for its regenerative slowpropagationdownthe 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 studywe examined themechanisms 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 elongationwere 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 (1-2mm) 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.

Original languageEnglish (US)
Pages (from-to)2919-2934
Number of pages16
JournalJournal of Physiology
Volume588
Issue number15
DOIs
StatePublished - Aug 2010
Externally publishedYes

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ASJC Scopus subject areas

  • Physiology
  • Medicine(all)

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