The origin of segmentation motor activity in the intestine

Abstract

The segmentation motor activity of the gut that facilitates absorption of nutrients, was first described in the late 19th century but the fundamental mechanisms underlying it remain poorly understood. The dominant theory suggests alternate excitation and inhibition from the enteric nervous system. Here we demonstrate that typical segmentation can occur after total nerve blockade. The segmentation motor pattern emerges when the amplitude of the dominant pacemaker, the slow wave generated by ICC associated with the myenteric plexus (ICC-MP), is modulated by the phase of induced lower frequency rhythmic transient depolarizations, generated by ICC associated with the deep muscular plexus (ICC-DMP), resulting in a waxing and waning of the amplitude of the slow wave and a rhythmic checkered pattern of segmentation motor activity. Phase amplitude modulation of the slow waves points to an underlying system of coupled nonlinear oscillators originating in ICC.

Neurotensin Changes Propulsive Activity into a Segmental Motor Pattern in the Rat Colon

“…Strain gauges showed propulsive contractions that changed into stationary contractions after intravenous injection of neurotensin. Using spatio-temporal mapping, we showed that the segmentation motor pattern in the mouse intestine has a checkered appearance, 35 identical to that described by Cannon. 42 Segmentation in the small intestine is caused by interactions of 2 pacemaker activities.…”

“…In the small intestine, the classical segmentation motor activity is generated when the ICC associated with the deep muscular plexus (ICC-DMP) produce a stimulus-dependent rhythmic electrical activity. 34,35 In the rat colon, it is the ICC-MP that generates a stimulus-dependent low frequency activity; the laboratories of Jimenez in the rat 31 and Takaki in the mouse 36 showed that ICC-MP are associated with a low frequency pacemaker that can drive contractions at frequencies from 0.3 to 2 cpm, 19,21,22,[31][32][33] hence the on/off pattern observed in the present study is likely to be associated with pacemaking from the ICC-MP. It is not known where the ultra-slow pacemaker that drives the slow propagating segmental contractions is located; it may be within the ENS or in the intramuscular ICC (ICC-IM).…”

“…19,22 They can occur in an apparent random fashion or they can appear highly organized in a checkered pattern that is most prominently observed in the small intestine. 35,46 The motor pattern described here as slow propagating segmental contraction is different in that it shows very clear rhythmicity and it shows propagation characteristics. We have also seen this pattern in response to granisetron, we described this as sequential segmental contractions 19 ; from now on we will describe this motor pattern as slow propagating segmental contractions or haustral boundary contractions.…”

“…42 Segmentation in the small intestine is caused by interactions of 2 pacemaker activities. 35 One is the myogenic pacemaker of the ICC-MP, the other a stimulus-dependent pacemaker of the ICC-DMP. We have shown that substance P can evoke the ICC-DMP pacemaker.…”

Optical Tools to Investigate Cellular Activity in the Intestinal Wall

“…110,111 Also, our understanding of myogenic and other mesenchymal control elements present in the gut wall, has improved based on imaging results. For example, recent reports show that interstitial cells of Cajal can operate independently from enteric neurons to control segmentation motor activity, 112 and need the Ca 2+ -activated Cl − channel Ano1 to coordinate slow waves in the smooth muscle. 113 Another recent study used Oregon Green BAPTA-2 as a Ca 2+ indicator to investigate the involvement of platelet derived growth factor receptor  (PDGFR + ) cells in inhibitory neurostransmission to smooth muscle cells.…”