Coordinated propagation of electrical activity is an underlying mechanism which regulates gastrointestinal (GI) motility. This investigation will measure components of electrical conduction and identify the degree to which various transmitters and conditions can regulate the propagation of electrical activity in GI muscles. The regions which will be studied, stomach antrum and gastroduodenal sphincter, play an important functional role in the coordinated generation of mechanical forces in the GI tract. The long-term goal of these studies will be to relate the regulation of electrical activity with the work performed by these muscles. The techniques to be used involve simultaneous, multi-electrode, electrophysiological recordings to monitor the rate of propagation at various sites on in vitro sheets of canine tissue. Studies will be performed in vitro i) to control hormonal and neural inputs, ii) to investigate the contribution of one muscle layer at a time, and iii) to carefully control muscle fiber orientation during measurements. Conduction velocities will be measured independently in each direction in tissues and at numerous sites across junctions. The dependence of conduction velocities will be measured in response to changes in pH, temperature and osmolarity (physical factors which can vary under physiological conditions). The dependence of conduction velocities will also be measured in response to transmitters, peptides and hormones normally found in the GI tract: acetylcholine, neurotensin, vasointestinal peptide and gastrin. The effects of slow wave frequency on conduction will be studied using a novel technique to characterize the frequency response of tissues. The dependence of the frequency response on the extracellular concentration of calcium and pH will be quantitated. The effects of trauma will be studied by inducing a controlled, localized injury. Data from these studies will form the basis of a quantitative, numerical model (simulation) to describe the spread of electrical activity in uniform and nonuniform regions of the GI tract. This investigation will address the basic mechanisms of cell-to-cell propagation during normal conduction and during conditions which result in motility disorders.
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