Selective knockout of intramuscular interstitial cells reveals their role in the generation of slow waves in mouse stomach.

1. Intracellular recording techniques were used to compare the patterns of electrical activity generated in the antral region of the stomachs of wild-type and W/W(V) mutant mice. Immunohistochemical techniques were used to determine the distribution of c-kit-positive interstitial cells of Cajal (ICC) within the same region of the stomach. 2. In wild-type mice interstitial cells were found at the level of the myenteric plexus (ICC(MY)) and distributed within the smooth muscle bundles (ICC(IM)). In these preparations slow waves, which consisted of initial and secondary components, were detected. 3. In W/WV mutant mice ICC(MY) could be identified at the level of the myenteric plexus but ICC(IM) were not detected within smooth muscle bundles. Intracellular recordings revealed that smooth muscle cells generated waves of depolarization; these lacked a secondary component. 4. These results indicate that the secondary regenerative component of a slow wave is generated by ICC(IM). Thus the depolarization arising from the pacemaker cells, ICC(MY), is augmented by ICC(IM), so causing a substantial membrane depolarization in the circular muscle layer. Rather than contributing directly to rhythmical electrical activity, smooth muscle cells appear to depolarize at the command of the two subpopulations of ICC.