The myogenic and neurogenic components of the rhythmic segmentation motor patterns of the intestine

Almost all motor patterns in gut organs have as primary function the mixing of content. Although classical peristalsis is equated with propulsion, and this is certainly the case in the esophagus, the predominant effect in all other organs is mixing and exposing the content optimally to the mucosal surface, because the propulsion ends somewhere and the content is moving back; only very rarely does propulsion end with evacuation of content from the body. The segmentation motor pattern is different from peristalsis in that it contains only stationary or very short distance propagating contractions and hence is considered a specialized motor pattern for mixing and absorption. The segmentation motor pattern was described and illustrated by Cannon in 1902 based on X-ray observations and shown to be extremely rhythmic (Cannon, 1902). Alvarez was the first to find that the frequency of rhythmic segmenting contractions occurred at the frequency of a myogenic pacemaker and that in various regions of the intestine the frequency decreased in the same way as the pacemaker frequency decreased (Alvarez, 1914), suggesting a firm relationship between slow waves and segmentation. In 1968, Code and co-workers also recognized the role of slow waves in segmentation (Code et al., 1968); the slow waves were thought to go in and out of excitable regions of smooth muscle fibers. Ehrlein noted in 1987 that there were no electrical or mechanical features known that could distinguish peristaltic and segmental motor patterns (Ehrlein et al., 1987). In 2006, two major reviews on control of motility only very briefly mentioned segmentation: “The most basic small intestinal contractile pattern, segmentation, results from reciprocal inhibition and dis-inhibition of adjacent circular muscle” (Hasler, 2006) and “Oscillation of membrane potential through the slow wave cycle results in periods of high and low open probability for Ca2+ channels, and this naturally organizes the contractile pattern into a series of phasic contractions contributing to motility patterns such as peristalsis and segmentation” (Sanders et al., 2006). Recently, it was shown that spontaneous segmentation or decanoic acid-induced segmentation is associated with a waxing and waning of the slow wave activity that can occur prominently in the presence of nerve conduction block (Huizinga et al., 2014). Evidence was provided that waxing and waning developed when low frequency rhythmic transient depolarizations originating from interstitial cells of Cajal (ICC) associated with the deep muscular plexus (ICC-DMP) interacted with the omnipresent slow wave activity originating from ICC associated with the myenteric plexus (ICC-MP) through phase–amplitude coupling. That is, the phase of the low frequency activity modulated the amplitude of the higher frequency slow wave activity. Hence interacting myogenic electrical activities were seen to underlie the segmentation motor pattern. The segmentation motor pattern appeared to be associated with the induction of a low frequency component, causing minute rhythm clusters of contractions and a waxing and waning of the amplitudes of the individual contractions within a cluster (Huizinga et al., 2014). These clusters occurred prominently after decanoic acid in rats (Huizinga et al., 2014) or oleic acid in dogs (Ehrlein et al., 1987). In human small intestine studies, the post-prandial motility pattern can be quite variable but regular “cluster contractions” are often reported and seen to be mainly stationary (Hellstrom, 1995). In a study by Husebye (1999), the clusters were shown to have a minute rhythm, the contraction amplitudes within the clusters had a waxing and waning appearance with a frequency of ~10/min, hence occurring at the slow wave frequency (Husebye, 1999; Gallego et al., 2014). When a nutrient solution was given to healthy volunteers with or without 40 g/l ethanol, it was ethanol in particular that induced a low frequency component, the clustered contractions; the clusters occurred at 1 per 2–3 min and the individual contractions within the clusters at ~12/min with waxing and waning amplitudes (Schmidt et al., 1997). Hence also in the human small intestine, the slow wave frequency, as well as an additional lower frequency component, are reported in the post-prandial intestinal motor activity.