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Publication : Ca<sup>2+</sup> signaling driving pacemaker activity in submucosal interstitial cells of Cajal in the murine colon.

First Author  Baker SA Year  2021
Journal  Elife Volume  10
PubMed ID  33399536 Mgi Jnum  J:313861
Mgi Id  MGI:6803254 Doi  10.7554/eLife.64099
Citation  Baker SA, et al. (2021) Ca(2+) signaling driving pacemaker activity in submucosal interstitial cells of Cajal in the murine colon. Elife 10:e64099
abstractText  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 Ca(2+) signaling in ICC-SM and the relationship between ICC-SM Ca(2+) transients and activation of smooth muscle cells (SMCs) using optogenetic tools. ICC-SM displayed rhythmic firing of Ca(2+)transients ~ 15 cpm and paced adjacent SMCs. The majority of spontaneous activity occurred in regular Ca(2+) transients clusters (CTCs) that propagated through the network. CTCs were organized and dependent upon Ca(2+) entry through voltage-dependent Ca(2+) conductances, L- and T-type Ca(2+) channels. Removal of Ca(2+) from the external solution abolished CTCs. Ca(2+) release mechanisms reduced the duration and amplitude of Ca(2+) transients but did not block CTCs. These data reveal how colonic pacemaker ICC-SM exhibit complex Ca(2+-)firing patterns and drive smooth muscle activity and overall colonic contractions.
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