Control of intrinsic pacemaker frequency and velocity of colonic migrating motor complexes in mouse

Abstract

The mechanisms that control the frequency and propagation velocity of colonic migrating motor complexes (CMMCs) in mammals are poorly understood. Previous in vitro studies on whole mouse colon have shown that CMMCs occur frequently (~every 1–3 min) when the colon is devoid of all fecal content. Consequently, these studies have concluded that the generation of CMMCs and the frequency which they occur does not require the presence of fecal content in the lumen. However, in these studies, stimuli have always been unavoidably applied to these empty colonic preparations, facilitating recordings of CMMC activity. We tested whether CMMCs still occur in empty whole colonic preparations, but when conventional recording methods are not used. To test this, we used video imaging, but did not utilize standard recording methods. In whole isolated colons containing multiple endogenous fecal pellets, CMMCs occurred frequently (1.9 ± 0.1/min) and propagated at 2.2 ± 0.2 mm/s. Surprisingly, when these preparations had expelled all content, CMMCs were absent in 11/24 preparations. In the remaining preparations, CMMCs occurred rarely (0.18 ± 0.02/min) and at reduced velocities (0.71 ± 0.1 mm/s), with reduced extent of propagation. When conventional recording techniques were then applied to these empty preparations, CMMC frequency significantly increased, as did the extent of propagation and velocity. We show that in contrast to popular belief, CMMCs either do not occur when the colon is free of luminal contents, or, they occur at significantly lower frequencies. We believe that previous in vitro studies on empty segments of whole mouse colon have consistently demonstrated CMMCs at high frequencies because conventional recording techniques stimulate the colon. This study shows that CMMCs are normally absent, or infrequent in an empty colon, but their frequency increases substantially when fecal content is present, or, if in vitro techniques are used that stimulate the intestine.

High‐resolution colonic motility recordings in vivo compared with ex vivo recordings after colectomy, in patients with slow transit constipation

“…In experimental animals, motor patterns comparable to human HAPS can be evoked by mechanical distension (with either fluid or solid content) in ex vivo preparations . For example, the frequency of colonic migrating motor complexes in the mouse colon increases when they are recorded by force transducers that put the gut wall under tension . Therefore, distension may play a critical role in the generation of HAPSs.…”

Neuromechanical factors involved in the formation and propulsion of fecal pellets in the guinea‐pig colon

“…The question as to whether proximal and distal CMMC are due to spontaneous, cyclic activity of enteric circuits that occur in the absence of any mechanical stimuli or whether they require some ongoing weak sensory input, and different mechanosensory sensory neurons is being debated . However, the formation and propulsion of liquid or more viscous pellets was blocked by hexamethonium, indicating that enteric cholinergic synaptic transmission is involved in the formation and propulsion of all fluid boluses.…”

“…These propulsive waves are usually described as peristalsis and there is a consensus that this is fundamentally an enteric neural process . In addition, neurally dependent, spontaneous contractions that slowly migrate aborally also occur in the non‐distended colon (‘colonic migrating motor complexes’ or CMMCs) . However, few studies have addressed the neurogenic and myogenic mechanisms underlying the formation of feces, their subsequent propulsion and the mechanical factors involved.…”

Characterizing colonic motility in children with chronic intractable constipation: a look beyond high‐amplitude propagating sequences

“…These have been variably described as discrete clustered contractions in the small intestine or colonic migrating motor complexes . They appear to occur even in the empty mouse colon …”