Author: Simona Elisa Carbone
Carbone, Simona Elisa, 2013 A FUNCTIONAL ANALYSIS OF GASTROINTESTINAL MOTILITY IN THE GUINEA PIG AND HUMAN, Flinders University, School of Medicine
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Gastrointestinal motility results from coordinated contractions and relaxation of smooth muscle layers of the gut wall. Motor patterns mix or propel content along the gastrointestinal tract. The circular and longitudinal muscle layers within the gut wall are comprised of smooth muscle cells and interstitial cells of Cajal (ICC), which work together to make up the myogenic component of gastrointestinal motility. Smooth muscle cells and ICC are electrically and metabolically coupled to themselves and each other by a series of gap junctions. Gap junction coupling has been shown in several cellular systems to be modulated by: pH, Ca2+, second messengers, voltage differences and by various neurotransmitters and pharmacological agents. Gastrointestinal motility is also controlled by intrinsic and extrinsic neural inputs. Mechanical and/or electrical recordings of smooth muscle cells from segments of the gut wall have been extensively studied in vitro to understand mechanisms underlying gastrointestinal motility. Immediately following setup, many of these preparations display a curious physiological feature: they appear to be completely inactive. These preparations lack tone, they fail to develop spontaneous contractions, they lack excitatory or inhibitory junction potentials, and these preparations fail to respond to electrical or pharmacological stimuli. Responses develop and then stabilise over the next 60-120 minutes. This phenomena is often implicitly reported in the methods section of papers, however the mechanistic causes for the apparent loss of responsiveness is unknown. One of the aims of this project was to understand the mechanisms that account for the loss of responses after dissection. In chapter 2, the electrical properties of circular smooth muscle cells from specimens of guinea pig ileum and colon were monitored as preparations recovered from dissection. Junction potentials (primarily fast inhibitory junction potentials), resting membrane potential, input resistance and dye coupling were monitored over this period. The role of gap junction coupling in neuromuscular transmission was investigated in chapter 3. In chapter 4, the role of various elements of the setup procedure were studied, in an attempt to highlight which factors activated the uncoupling process. This problem was approached from 2 directions: by testing whether manipulations could evoke a second loss of response, and by testing whether omitting the use of other manipulations reduced the initial loss of responses. In chapter 5 the role of cholingeric interneuronal pathways in generating an ascending contraction in segments of human colon was studied. Few functional in vitro studies have considered the role of interneural pathways in human tissue due to limited supply of specimens of an appropriate size required for this analysis. The frequency of spontaneous contractions in narrow segments versus larger segments was also considered. These studies identified two mechanisms that may contribute to the control of gastrointestinal motility in vitro. Their physiological significance in vitro remains to be determined.
Keywords: smooth muscle,enteric nervous system,intestine,human,guinea pig
Subject: Human Physiology thesis, Medicine thesis
Thesis type: Doctor of Philosophy
School: School of Medicine
Supervisor: Simon Brookes