Motor patterns of the small intestine explained by phase-amplitude coupling of two pacemaker activities: the critical importance of propagation velocity

Abstract

Phase-amplitude coupling of two pacemaker activities of the small intestine, the omnipresent slow wave activity generated by interstitial cells of Cajal of the myenteric plexus (ICC-MP) and the stimulus-dependent rhythmic transient depolarizations generated by ICC of the deep muscular plexus (ICC-DMP), was recently hypothesized to underlie the orchestration of the segmentation motor pattern. The aim of the present study was to increase our understanding of phase-amplitude coupling through modeling. In particular the importance of propagation velocity of the ICC-DMP component was investigated. The outcome of the modeling was compared with motor patterns recorded from the rat or mouse intestine from which propagation velocities within the different patterns were measured. The results show that the classical segmentation motor pattern occurs when the ICC-DMP component has a low propagation velocity (<0.05 cm/s). When the ICC-DMP component has a propagation velocity in the same order of magnitude as that of the slow wave activity (∼1 cm/s), cluster type propulsive activity occurs which is in fact the dominant propulsive activity of the intestine. Hence, the only difference between the generation of propagating cluster contractions and the Cannon-type segmentation motor pattern is the propagation velocity of the low-frequency component, the rhythmic transient depolarizations originating from the ICC-DMP. Importantly, the proposed mechanism explains why both motor patterns have distinct rhythmic waxing and waning of the amplitude of contractions. The hypothesis is brought forward that the velocity is modulated by neural regulation of gap junction conductance within the ICC-DMP network.