Study on function of aganglionic colon musculature of hirschsprung's disease murine model.

Abstract

This study examined the function in vitro of aganglionic colon musculature in mice with hereditary aganglionosis--a strain of animals used as a model of Hirschsprung's disease. Double sucrose gap recordings from the muscle strips of both normal and aganglionic colon showed bursts of spike potentials with muscle contraction. Intracellular recordings of the membrane potentials of the circular muscle cells of normal, aganglionic and oligo-ganglionic colon had no statistical difference. Microelectrode recordings from the circular muscle cells of normal siblings, in the presence of nifedipine, irregular ongoing fluctuations in membrane potential, which were abolished by tetrodotoxin and reduced by d-tubocurarine or apamin. The fluctuations were less effected by atropine. These observations suggest that there is ongoing inhibitory neural activity to the circular smooth muscle of normal colon. These ongoing fluctuations were not recorded from the cells of aganglionic and oligo-ganglionic colon of affected animals. Although transmural stimulation of the intrinsic nerves produced cholinergic excitatory and inhibitory junction potentials in normal colon, no junction potentials were evoked by transmural stimulation in aganglionic colon. It was concluded that the ongoing tonic inhibitory activity may contribute to the compliance of the normal mouse colon and lack of the compliance may affect functional intestinal obstruction of the aganglionic colon in Hirschsprung's disease.