Spontaneous electrical rhythmicity in cultured interstitial cells of Cajalfrom the murine small intestine

1. Interstitial cells of Cajal (ICC) are pacemaker cells in the small bowel , and therefore this cell type must express the mechanism responsible for s low wave activity. Isolated ICC were cultured for 1-3 days from the murine small intestine and identified with c-Kit-like immunoreactivity (c-Kit-LI). 2. Electrical recordings were obtained from cultured ICC with the whole-cel l patch clamp technique. ICC were rhythmically active, producing regular sl ow wave depolarizations with waveforms and properties similar to slow waves in intact tissues. 3. Spontaneous activity of c-Kit-LI cells was inhibited by reduced extracel lular Na+, gadolinium, and reduced extracellular Ca2+. The activity was not affected by nisoldipine. Voltage clamp studies showed rhythmic inward curr ents that were probably responsible for the slow wave activity. The current -voltage relationship showed that the spontaneous currents reversed at abou t +17 mV. These observations are consistent with the involvement of a non-s elective cation current in the generation of slow waves, but do not rule ou t contributions from other conductances or transporters. 4. A Ba2+-sensitive inwardly rectifying K+ current in c-Kit-LI cells that m ay be involved ill slow wave repolarization and maintenance of a negative p otential between slow waves was also found. Similar pharmacology was observ ed in studies of intact murine intestinal muscles. 5. Cultured ICC may be a useful model for studying the properties and pharm acology of some of the ionic conductances involved in spontaneous rhythmici ty in the gastrointestinal tract.