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bioRxiv · 10.1101/2020.10.26.355404

Ca2+ signaling driving pacemaker activity in submucosal interstitial cells of Cajal in the colon

Baker, S.·Leigh, W. A.·De Yturriaga, I. F.·Ward, S. M.·Cobine, C. A.·Drumm, B. T.·Sanders, K.
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Abstract

Interstitial cells of Cajal (ICC) generate pacemaker activity responsible for phasic contractions in colonic segmentation and peristalsis. ICC along the submucosal border (ICC-SM) contributing 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 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. SynopsisHow Ca2+ signaling in colonic submucosal pacemaker cells couples to smooth muscle responses is unknown. This study shows how ICC modulate colonic motility via complex Ca2+ signaling and defines Ca2+ transients sources using optogenetic techniques.

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Baker, S., Leigh, W. A., De Yturriaga, I. F., Ward, S. M., Cobine, C. A., Drumm, B. T., Sanders, K.. 2020-10-26. Ca2+ signaling driving pacemaker activity in submucosal interstitial cells of Cajal in the colon. https://doi.org/10.1101/2020.10.26.355404

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