Interstitial cells of Cajal generate electrical slow waves in the murine stomach

1. The gastric corpus and antrum contain interstitial cells of Cajal (ICC) within the tunica muscularis. We tested the hypothesis that ICC are involve d in the generation and regeneration of electrical slow waves. 2. Normal, postnatal development of slow wave activity mas characterized in tissues freshly removed from animals between birth and day 50 (D50). Slow wave amplitude and frequency increased during this period. Networks of myen teric ICC (IC-MY) were present in gastric muscles at birth and did not chan ge significantly in appearance during the period of study as imaged by conf ocal immunofluorescence microscopy, 3. IC-MY networks were maintained and electrical rhythmicity developed in o rgan culture in a manner similar to nor mal postnatal development. Electric al activity was maintained for at least 48 days in culture. 4. Addition of a neutralizing antibody (ACK2) for, the receptor tyrosine ki nase, Kit, to the culture media caused progressive loss of Kit-immunoreacti ve cells. Loss of Kit-immune reactive cells was associated with loss of slo w wave activity. Most muscles became electrically quiescent after 3-4 weeks of exposure to ACK2. 5. In some muscles small clusters of Kit-immunoreactive IC-MY remained afte r culturing with ACK2. These muscles displayed slow wave activity hut only in the immediate regions in which Kit-positive IC-MY remained. These data s uggest that regions without Kit-immunoreactive cells cannot generate or reg enerate slow waves. 6. After loss of Kit-immunoreactive cells, the muscles could not be paced b y direct electrical stimulation. Stimulation with acetylcholine also failed to elicit slow waves. The data suggest that the generation of slow waves i s an exclusive property of IC-MY; smooth muscle cells may not express the i onic apparatus necessary for generation of these events. 7. We conclude that IC-MY are an essential element in the spontaneous rhyth mic electrical and contractile activity of gastric muscles. This class of I CC appears to generate slow wave activity and may provide a means for regen eration of slow waves.