Abstract
These studies were directed toward better characterization of the abnormalities of motor function in the large intestine of mutant mice with congenital aganglionosis and megacolon. Analysis of pressure-volume relations in the megacolon and aganglionic terminal segment showed increased intestinal wall compliance in the dilated colon and reduced wall compliance in the aganglionic region as compared to normal littermates. Migrating contractile complexes occurred spontaneously in ganglionated regions of the large intestine of both normal and mutant mice, but never propagated into the aganglionic segment of the abnormal bowel. Tetrodotoxin eliminated the migrating complexes and increased random spontaneous contractions in all areas except the aganglionic region. Circular muscle tension was reduced by electrical field stimulation, and poststimulus rebound contractions occurred in all ganglionated regions of the intestine of both normal and mutant mice. No responses to electrical stimulation occurred in the aganglionic segments of the preparations from mutant mice. The poststimulus responses “fatigued” at a faster rate in the megacolonic region of the abnormal bowel than in the equivalent region of the normal bowel, when evoked repetitively over prolonged time periods. There were no differences between the intestines of normal and mutant mice in latency, amplitude, duration, or area under the contractile curves of the poststimulus responses. Intracellular electrical recording from circular muscle fibers revealed slow depolarizing potentials with action potentials at the crests in all regions of the large bowel from both normal and abnormal mice. It also showed excitatory and inhibitory junction potentials in response to electrical stimulation. Inhibitory junction potentials summated during repetitive stimulation and postinhibitory rebound excitation occurred after offset of the stimulation. Stimulus-evoked junction potentials were recorded in all regions of the large intestine except in the aganglionic segment of the mutant mice. We concluded that most of the electrical and mechanical behavior of the aganglionic terminal segment reflected the absence of inhibitory innervation of the musculature in this region.
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Supported by NIH RO1 AM26742.
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Wood, J.D., Brann, L.R. & Vermillion, D.L. Electrical and contractile behavior of large intestinal musculature of piebald mouse model for Hirschsprung's disease. Digest Dis Sci 31, 638–650 (1986). https://doi.org/10.1007/BF01318696
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DOI: https://doi.org/10.1007/BF01318696