The long term goals of this work are to understand the function of submucous plexus neurons throughout the gastrointestinal (GI) tract. All submucous plexus neurons project to the intestinal mucosa or to each other; thus they may play a major role in controlling or modulating fluid and electrolyte transport in the intestine. Intracellular recordings of membrane voltage and membrane current, using single-electrode voltage clamp techniques, will be obtained from submucous neurons of the guinea-pig small intestine to elucidate the mechanisms of actions of neuropeptides and other putative transmitter substances on the postsynaptic membrane. Patterns of neuronal circuitry will be investigated by selective disruption of pathways to the submucous plexus by carrying our extrinsic denervations, myectomies, and myotomies in combination with electrophysiological studies of the alterations in synaptic input to the lesioned plexus preparation. Mechanisms of synaptic transmission in submucous neurons of the descending colon will be studied in order to investigate the role these neurons may play in the region of the GI tract which is the major site of net fluid and electrolyte absorption. Dysfunction of the neurons of the submucous plexus may be involved with several pathophysiological states, such as as carcinoid syndrome, dumping syndrome and diabetic diarrhea. Knowledge of the functions of these neurons should provide insight into mechanisms underlying these disease states and, potentially, insight into therapeutic means of their control.
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