Interstitial cells of cajal direct normal propulsive contractile activity in the mouse small intestine.

BACKGROUND & AIMS: Interstitial cells of Cajal (ICC) have been linked to the generation of intestinal pacemaker activity, but their role in in vivo motor dysfunction is unclear. In this study, we investigated the hypothesis that ICC play a role in the generation of distention-induced peristalsis using W/Wv mice that lack ICC associated with Auerbach's plexus. METHODS: Radiological observations were made of the movement of contrast fluid through the proximal small intestine. Electrical activities were recorded in the external muscle layers. In addition, intraluminal pressure changes were recorded in isolated intestinal segments. RESULTS: In control mice, after gavage of 0.5 mL of barium sulfate in the stomach, the contrast fluid moved through the proximal small intestine in peristaltic waves at approximately 47 times a minute, propagating aborally at approximately 2 cm/s. Electrical slow waves and intraluminal pressure waves were synchronized at similar frequencies and propagation velocities. In W/Wv mice, such regular peristaltic waves were not observed. Action potentials and contractions appeared random, and contents moved back and forth in an irregular manner. The net propulsive effect of contractile activity in W/Wv mutant mice was much weaker than that in controls. CONCLUSIONS: Slow wave controlled peristalsis occurs in the normal proximal small intestine upon gastric emptying of a semiliquid. This motor pattern is absent in W/Wv mice that lack ICC.

Co-operation between neural and myogenic mechanisms in the control of distension-induced peristalsis in the mouse small intestine.

1. Myogenic and neural control of intestinal transit were investigated in a model of distension-induced peristalsis. A comparison was made between the electrical and mechanical activities and outflow of contents observed in control mice and in W/Wv mice, which lack the interstitial cells of Cajal associated with Auerbach's plexus. 2. Distension caused a periodic appearance of increased motor activity due to stimulation of enteric nerves in both control and W/Wv mice. Excitation was primarily delivered by cholinergic nerves, whereas periodic inhibition was mediated by neuronal nitric oxide. 3. In control mice, outflow was driven by propagating slow-wave activity and was only in the aboral direction. Outflow only occurred when slow waves carried sufficient action potentials to cause phasic intraluminal pressure increases of > or = 1 cm H2O through direct stimulation of the musculature or by distension-induced neurally mediated activation. 4. In W/Wv mice, outflow was associated with propagating action potentials that occurred due to either neural stimulation or direct muscle stimulation. Action potential propagation and outflow occurred in both oral and aboral directions. 5. In summary, in both control and W/Wv mice, distension induced periodic motor activity through stimulation of the enteric nervous system. Intraluminal contents were not moved in front of such motor activity. Rather, within such periods of activity that occurred concurrently throughout an entire segment, pulsatile outflow was directed by individual propagating slow waves with superimposed action potentials in control tissue, and by propagating action potentials in W/Wv mice, which lack interstitial cells of Cajal.