Ca2+ signaling driving pacemaker activity in submucosal interstitial cells of Cajal in the murine colon
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 IC...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2021-01-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/64099 |
| _version_ | 1818019586113536000 |
|---|---|
| author | Salah A Baker Wesley A Leigh Guillermo Del Valle Inigo F De Yturriaga Sean M Ward Caroline A Cobine Bernard T Drumm Kenton M Sanders |
| author_facet | Salah A Baker Wesley A Leigh Guillermo Del Valle Inigo F De Yturriaga Sean M Ward Caroline A Cobine Bernard T Drumm Kenton M Sanders |
| author_sort | Salah A Baker |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-14T07:54:18Z |
| format | Article |
| id | doaj.art-df4a3be70d6747c38f6b141798f6b25d |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-14T07:54:18Z |
| publishDate | 2021-01-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-df4a3be70d6747c38f6b141798f6b25d2022-12-22T02:05:06ZengeLife Sciences Publications LtdeLife2050-084X2021-01-011010.7554/eLife.64099Ca2+ signaling driving pacemaker activity in submucosal interstitial cells of Cajal in the murine colonSalah A Baker0https://orcid.org/0000-0002-1514-6876Wesley A Leigh1Guillermo Del Valle2Inigo F De Yturriaga3Sean M Ward4Caroline A Cobine5Bernard T Drumm6Kenton M Sanders7Department of Physiology and Cell Biology, University of Nevada, Reno, School of Medicine, Reno, United StatesDepartment of Physiology and Cell Biology, University of Nevada, Reno, School of Medicine, Reno, United StatesDepartment of Physiology and Cell Biology, University of Nevada, Reno, School of Medicine, Reno, United StatesDepartment of Physiology and Cell Biology, University of Nevada, Reno, School of Medicine, Reno, United StatesDepartment of Physiology and Cell Biology, University of Nevada, Reno, School of Medicine, Reno, United StatesDepartment of Physiology and Cell Biology, University of Nevada, Reno, School of Medicine, Reno, United StatesDepartment of Physiology and Cell Biology, University of Nevada, Reno, School of Medicine, Reno, United StatesDepartment of Physiology and Cell Biology, University of Nevada, Reno, School of Medicine, Reno, United StatesInterstitial 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.https://elifesciences.org/articles/64099pacemakerslow wavesca2+ entryca2+-induced ca2+ releasegi motilityca2+ signaling |
| spellingShingle | Salah A Baker Wesley A Leigh Guillermo Del Valle Inigo F De Yturriaga Sean M Ward Caroline A Cobine Bernard T Drumm Kenton M Sanders Ca2+ signaling driving pacemaker activity in submucosal interstitial cells of Cajal in the murine colon eLife pacemaker slow waves ca2+ entry ca2+-induced ca2+ release gi motility ca2+ signaling |
| title | Ca2+ signaling driving pacemaker activity in submucosal interstitial cells of Cajal in the murine colon |
| title_full | Ca2+ signaling driving pacemaker activity in submucosal interstitial cells of Cajal in the murine colon |
| title_fullStr | Ca2+ signaling driving pacemaker activity in submucosal interstitial cells of Cajal in the murine colon |
| title_full_unstemmed | Ca2+ signaling driving pacemaker activity in submucosal interstitial cells of Cajal in the murine colon |
| title_short | Ca2+ signaling driving pacemaker activity in submucosal interstitial cells of Cajal in the murine colon |
| title_sort | ca2 signaling driving pacemaker activity in submucosal interstitial cells of cajal in the murine colon |
| topic | pacemaker slow waves ca2+ entry ca2+-induced ca2+ release gi motility ca2+ signaling |
| url | https://elifesciences.org/articles/64099 |
| work_keys_str_mv | AT salahabaker ca2signalingdrivingpacemakeractivityinsubmucosalinterstitialcellsofcajalinthemurinecolon AT wesleyaleigh ca2signalingdrivingpacemakeractivityinsubmucosalinterstitialcellsofcajalinthemurinecolon AT guillermodelvalle ca2signalingdrivingpacemakeractivityinsubmucosalinterstitialcellsofcajalinthemurinecolon AT inigofdeyturriaga ca2signalingdrivingpacemakeractivityinsubmucosalinterstitialcellsofcajalinthemurinecolon AT seanmward ca2signalingdrivingpacemakeractivityinsubmucosalinterstitialcellsofcajalinthemurinecolon AT carolineacobine ca2signalingdrivingpacemakeractivityinsubmucosalinterstitialcellsofcajalinthemurinecolon AT bernardtdrumm ca2signalingdrivingpacemakeractivityinsubmucosalinterstitialcellsofcajalinthemurinecolon AT kentonmsanders ca2signalingdrivingpacemakeractivityinsubmucosalinterstitialcellsofcajalinthemurinecolon |