TY - JOUR TI - Ca2+ signaling driving pacemaker activity in submucosal interstitial cells of Cajal in the murine colon AU - Baker, Salah A AU - Leigh, Wesley A AU - Del Valle, Guillermo AU - De Yturriaga, Inigo F AU - Ward, Sean M AU - Cobine, Caroline A AU - Drumm, Bernard T AU - Sanders, Kenton M A2 - Nelson, Mark T A2 - Aldrich, Richard W A2 - Davis, Michael J VL - 10 PY - 2021 DA - 2021/01/05 SP - e64099 C1 - eLife 2021;10:e64099 DO - 10.7554/eLife.64099 UR - https://doi.org/10.7554/eLife.64099 AB - Interstitial cells of Cajal (ICC) generate pacemaker activity responsible for phasic contractions in colonic segmentation and peristalsis. ICC along the submucosal border (ICC-SM) contribute to mixing and more complex patterns of colonic motility. We show the complex patterns of Ca2+ signaling in ICC-SM and the relationship between ICC-SM Ca2+ transients and activation of smooth muscle cells (SMCs) using optogenetic tools. ICC-SM displayed rhythmic firing of Ca2+transients ~ 15 cpm and paced adjacent SMCs. The majority of spontaneous activity occurred in regular Ca2+ transients clusters (CTCs) that propagated through the network. CTCs were organized and dependent upon Ca2+ entry through voltage-dependent Ca2+ conductances, L- and T-type Ca2+ channels. Removal of Ca2+ from the external solution abolished CTCs. Ca2+ release mechanisms reduced the duration and amplitude of Ca2+ transients but did not block CTCs. These data reveal how colonic pacemaker ICC-SM exhibit complex Ca2+-firing patterns and drive smooth muscle activity and overall colonic contractions. KW - pacemaker KW - slow waves KW - ca2+ entry KW - ca2+-induced ca2+ release KW - gi motility KW - ca2+ signaling JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -