Date of Award

Fall 2012

Degree Type

Thesis

Degree Name

Master of Science (MSc)

Department

Physiology and Pharmacology

Supervisor

Jan D Huizinga

Language

English

Abstract

The organs of the gastrointestinal (GI) tract display a variety of motor patterns, involved in grinding, mixing, enhancing absorption and propulsion of nutrients and waste products. Specialized motor patterns are generated by unique mechanisms inherent to the GI segment in which they are found. Rhythmic contractions are a feature of most motor patterns. Slow wave driven peristalsis is an acknowledged motor pattern associated with interstitial cells of Cajal (ICC) pacemakers, but propulsive motor patterns which are blocked by tetrodotoxin are seen to be exclusively generated by the enteric nervous system (ENS). This has not been proven, however, and the origin of rhythmicity of propulsive motor patterns needs further study, particularly related to a potential role of the pacemaker ICC found throughout the GI tract. The aim of this study was exploring the mechanisms which underlie various GI motor patterns, with particular focus on the origin of rhythmicity of these patterns.

I have demonstrated with manometry and spatiotemporal maps that murine rhythmic propulsion requires a myogenic pacemaker which is evoked by acetylcholine and substance P; nitric oxide is not involved. Calcium imaging evidence suggests that the pacemaker is the ICC of the deep muscular plexus, as these cells rhythmically activate to substance P. I observed rhythmic contractility patterns in human antrum, pylorus and duodenum when stimulated with carbachol. The hypothesis emerged that the ENS modifies the pyloric pacemaker into unique rhythmic patterns. Colonic muscle strip contractility from the rat has a low frequency rhythmic pattern which is myogenic. This pattern is augmented by the conditioned media from the probiotic E. coli Nissle 1917 through a non-neural mechanism.

The current explanation of entirely ENS generated motor patterns is not accurate. The ENS plays an important role in stimulating and regulating GI motor patterns in conjunction with myogenic pacemakers. It is only through acknowledgment of all GI cell types that we can understand the mechanisms governing motility.

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