The general objective of proposed research is to understand the mechanisms of rhythmic motility in the small intestine. Electrical activity is measured at three levels- from unanesthetized animals using implanted electrodes, from exteriorized intestinal loops of anesthetized cats using pressure and intracellular microelectrodes, and from isolated strips of smooth muscle using pressure and intracellular microelectrodes. Each method of measurement shows some differences in types of activity and for possible clinical applications, extrapolations from one level to another are needed. From implanted electrodes there have been recorded, in addition to spikes and migrating myoelectric complexes, two types of """"""""slow waves"""""""" - the invariant 16-18 per minute waves which have been much studied in vitro and more variant 20-30 per minute waves which may possibly be neurally initiated. Correlations of the newly discovered faster """"""""slow waves"""""""" with intestinal motility, locomotor activity, sleep, feeding and circadian rhythmicity will be sought. Various agonists and antagonists of putative neural transmitters will be injected via a catheter directly at recording sites. In anesthetized preparations, nerve stimulation and applications of drugs will be used. The basic rhythmic """"""""slow wave"""""""" which is metabolically controlled, persists in isolated preparations; its amplitude is determined by an electrogenic sodium pump, but its frequency control is unknown. Frequency appears to be determined by the level of intracellular calcium ions. A major cellular problem is the coupling between a voltage-dependent Ca++ channel and the Na-K pump. Several hypotheses for the coupling are to be tested, the most promising one involves cyclic nucleotides. Two clinically related projects are: (1) a search for the cellular mechanisms of proximal muscle hypertrophy and distal atrophy in obstructive ileus and (2) study of ionic control of both excitatory and inhibitory responses to mechanical disturbance of intestinal muscle.
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