The aim of this study is to delineate the neural pathways which control colonic electrical and mechanical activity in the in vitro dog colon. The working hypothesis is that neural control is compartmentalized, i.e., that different neuronal types have their greatest actions on the colonic smooth muscle at a particular location within the colon wall. For this study we will make both mechanical and intracellular measurements using various isolated sub-segments of the colon wall. The experiments will determine the characteristics of neuronal control at each location and evaluate where different enteric nerve types (i.e., cholinergic, noncholinergic excitatory and noncholinergic, nonadrenergic, inhibitory) exert their greatest effect. Enteric nerves will be activated with three different kinds of stimulation namely, 1) transmural stimulation 2) distention and 3) via extrinsic nerve stimulation. The experiments to be undertaken are divided into 4 categories, and are as follows: 1) Contractile studies. Contractile how nerves and putative transmitter substances alter this myogenic behavior. 2) Electrophysiological Mapping. These intracellular studies will describe the nature and location of junction potentials elicited in the smooth muscle with nerve stimulation and how these junction potentials alter the myogenic properties of the smooth muscle. 3) Applied Transmitter. These intracellular studies will involve application by spritzing techniques of known and putative transmitter substances to circumscribed portions of the colon. They will provide insight into the possible nature of the transmitters released by noncholinergic excitatory and inhibitory nerves and reveal the degree of uniformity in receptor type (or transduction mechanisms) across the wall of the colon. They will also investigate how known substances alter the basal myogenic activity of the smooth muscle. 4) Immunochistochemistry. These studies will correlate the morphological location of nerves with the physiological responses obtained in categories 1), 2) and 3). They will further address the question of localization of structure and function within the colon wall. The present study offers a new approach to understanding neural control of the colon y allowing one to attribute the actions of nerves to particular locations within the colon. These studies are of clinical importance in the treatment of disease processes which involve dysfunction of enteric nerves such as Hischsprung's disease.
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