Experiments are proposed to study the basic electrophysiology of canine pyloric sphincter. The electrical activity of the pylorus is complicated and has not been adequately described by previous extracellular recordings or by the few reported intracellular studies. We have developed cross-sectional preparations of the pyloric muscularis which allow precise placement of intracellular microelectrodes to characterize the electrical activity at any point within the pyloric ring or at any level through the thickness of the muscle. A complete analysis of pyloric electrical waveforms will be performed. Preliminary studies have revealed that pyloric muscles are paced by antral electrical activity and that much of the pylorus may be quiescent when it is uncoupled from the distal antrum. We have also observed that slow waves decay in amplitude as they propogate through the circular layer or distally through the pyloric ring. The bulk of the circular muscle of the pylorus appears to be a passive syncytium which does not generate or regenerate slow wave activity. This raises the question of how the pylorus is activated, and how its activity is coordinated with gastric peristaltic activity. Experiments to answer these questions will be performed. The origin and mechanisms of propagation of electrical events will be determined. We will also investigate regulation of electrical activity within the pylorus, specifically how neurotransmitters and hormonal influences affect spontaneous events and the propagation of electrical events. An initial hypothesis is that neural regulation controls the frequency of activity at the pacemaker sites more proximal to the pylorus, but the amplitude of electrical events and the extent of the spread of these events into the pyloric ring depends upon neural and hormonal conditioning of the syncytial cable properties and excitability mechanisms. We will also determine the relationship between electrical and mechanical events. Finally we will attempt to correlate electrophysiological characteristics with structural measurements. We hope to reconcile electrical responses to neural stimulation with measurements of innervation density and cable parameters to structural characteristics of the syncytium. These experiments should provide a basis for understanding the basic mechanisms controlling pyloric motility and help to explain the role of the pylorus in regulating gastric emptying.
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