Work

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

Year: 2021

Type: article

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 Ca 2+ signaling in ICC-SM and the relationship between ICC-SM Ca 2+ transients and activation of 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 Ca2+ 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. Synopsis How Ca 2+ signaling in colonic submucosal pacemaker cells couples to smooth muscle responses is unknown. This study shows how ICC modulate colonic motility via complex Ca 2+ signaling and defines Ca 2+ transients’ sources using optogenetic techniques.

Source: eLife

DOI: 10.7554/elife.64099