ON THE ORIGIN AND FUNCTION OF WAXING AND WANING IN PACEMAKER ACTIVITY IN THE SMALL INTESTINE

Abstract

<p>The small intestine of the gastrointestinal tract displays a variety of motor patterns involved in the mixing, digestion, and propulsion of luminal content. Ultimately, it is the co-ordinated effort of smooth muscle contraction influenced by neural and myogenic stimulation that facilitate these motor patterns. While neural input from the enteric nervous system (ENS) and slow wave producing activity of the peacemaking interstitial cells of Cajal (ICC) in the myenteric plexus (ICC-MP) are key players in the manipulation of smooth muscle cells, the mechanisms behind the onset the segmentation motor pattern are currently unknown. I have demonstrated with intracellular recordings of electrical activity from circular smooth muscle cells, the same nutrient stimulants used to induce the segmentation motor pattern in whole organ preparations evokes the waxing waning phenomenon of the smooth muscle slow wave. Through the use of continuous wavelet transformation analysis on nutrient induced waxing waning, it was determined that the induction of a rhythmic low frequency component is responsible for the generation of waxing waning. Stimulated low frequency activity after methylene blue mediated elimination of ICC-MP slow wave activity suggested the low frequency component did not originate from the ICC-MP. The hypothesis emerged that the ICC of the deep muscular plexus (ICC-DMP), on the opposite side of the circular muscle thickness to the ICC-MP, were responsible for the low frequency oscillations. ICC-DMP networks in close physical proximity to nerve fibers were found to be under tonic inhibited by nitric oxide, and to respond to substance P stimulation. Both alleviation of the inhibition and stimulus by tachykinergic neurotransmission induced the low frequency component and waxing waning. The ENS and myogenic pacemakers play an important role in stimulating the segmentation motor pattern. ICC-DMP are the pacemakers responsible for generation of the low frequency component involved in waxing waning and segmentation.</p>