Two Independent Networks of Interstitial Cells of Cajal Work Cooperatively with the Enteric Nervous System to Create Colonic Motor Patterns

Abstract

Normal motility of the colon is critical for quality of life and efforts to normalize abnormal colon function have had limited success. A better understanding of control systems of colonic motility is therefore essential. We report here a hypothesis with supporting experimental data to explain the origin of rhythmic propulsive colonic motor activity induced by general distention. The theory holds that both networks of interstitial cells of Cajal (ICC), those associated with the submuscular plexus (ICC–SMP) and those associated with the myenteric plexus (ICC–MP), orchestrate propagating contractions as pacemaker cells in concert with the enteric nervous system (ENS). ICC–SMP generate an omnipresent slow wave activity that causes propagating but non-propulsive contractions (“rhythmic propagating ripples”) enhancing absorption. The ICC–MP generate stimulus-dependent cyclic depolarizations propagating anally and directing propulsive activity (“rhythmic propulsive motor complexes”). The ENS is not essential for both rhythmic motor patterns since distention and pharmacological means can produce the motor patterns after blocking neural activity, but it supplies the primary stimulus in vivo. Supporting data come from studies on segments of the rat colon, simultaneously measuring motility through spatiotemporal mapping of video recordings, intraluminal pressure, and outflow measurements.

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

“…30 Also in the rat colon, the strongest myogenic pacemaker originates in the ICC-SMP, which is governing the ripples at 10-14 cpm, which can be seen to be part of all the motor patterns. 19,21,22,[31][32][33] They are clearly seen in the most proximal colon in between the LDCs in Figure 3B. They do not appear to be associated with the slow propagating segmental contractions.…”

“…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).…”

“…We and others recently reported that the CMMC contains 2 distinct propulsive motor patterns, a pancolonic long distance contraction (LDC) and a rhythmic propagating motor complex (RPMC) that is primarily observed in the mid and distal colon. [18][19][20][21][22] The objective of the present study was to understand how the inhibitory and excitatory actions of neurotensin translate into motor patterns of the whole colon in the rat. Interestingly, neurotensin consistently evoked a segmental motor pattern, slow propagating rhythmic haustral boundary contractions, that were rarely observed spontaneously.…”

Spatiotemporal Mapping of Motility in <em>Ex Vivo</em> Preparations of the Intestines

“…While these patterns were identified by earlier experimental methods, the current approach allows a more refined definition of localized contractile movements such as ripples and novel antiperistaltic contractions 9,24,25,30,31,42 . The construction of STmaps and analysis of changes in motility pattern have been applied to key questions in the gastrointestinal motility of intestine and colon.…”

“…Video recording and spatiotemporal mapping of intestinal and colonic segments have been applied to a variety of species including zebrafish 26 , mouse 25,[27][28][29][30] , rat 7,9,[30][31][32][33] , guinea pig 5,6,8,[13][14][15][16][17][18][19]24,30,32,34,35 , brushtail possum 12,36 , rabbit 2,30,37,38 , chicken 39 , pig 40,41 and human 42 . The most widely studied species is the guinea pig.…”