Simultaneous imaging of Ca2+ signals in interstitial cells of Cajal and longitudinal smooth muscle cells during rhythmic activity in mouse ileum

Electrical rhythmicity in smooth muscle cells is essential for the movement of the gastrointestinal tract. Interstitial cells of Cajal (ICC) lie adjacent to smooth muscle layers and are implicated as the pacemaker cells. However, the pace making mechanism remains unclear. To study the intercellular interaction during electrical rhythm generation, we visualized changes in intracellular Ca2+ concentration ([Ca2+](i)) in smooth muscle cells and myenteric ICC within segments of mouse ileum loaded with a fluorescent Ca2+ indicator, fluo-3. We observed rhythmic [Ca2+](i) changes in longitudinal smooth muscle cells travelling rapidly through the smooth muscle cell layer. Between the rhythmic Ca2+ transients, we found brief Ca2+ transients localized to small areas within smooth muscle cells. The amplitude but not the periodicity of rhythmic [Ca2+](i) transients in both cell types was partially inhibited by nicardipine, an L-type Ca2+ channel antagonist, suggesting that the rhythmic [Ca2+](i) transients reflect membrane potential depolarizations corresponding to both slow waves and triggered Ca2+ spikes. Longitudinal smooth muscle cells and myenteric ICC showed synchronous spontaneous [Ca2+](i) transients in eight out of 21 ileac preparations analysed. In the remaining preparations, the synchrony between ICC and smooth muscle cells was absent, although the rhythmicity of the smooth muscle cells was not disturbed. These results suggest that myenteric ICC may play multiple roles including pace making for physiological bowel movement.