{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T02:17:21Z","timestamp":1790561841450,"version":"4.1.0"},"reference-count":81,"publisher":"Wiley","license":[{"start":{"date-parts":[[2025,5,5]],"date-time":"2025-05-05T00:00:00Z","timestamp":1746403200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004765","name":"Honeywell Hometown Solutions","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004765","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK129528"],"award-info":[{"award-number":["DK129528"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"abstract":"Abstract<\/jats:title>The oesophagogastric junction (EGJ) is a high\u2010pressure zone consisting of the lower oesophageal sphincter (LES), distal oesophagus and crural diaphragm. Phasic electrical activity associated with phasic contractions has been demonstrated in the human distal oesophagus as well as in the dog proximal LES but is absent from the dog distal LES where phasic contractions are also absent. As electrical slow waves are dependent on activation of anoctamin 1 (ANO1) channels in interstitial cells of Cajal (ICC), we hypothesized that differences in contractile activity between regions may be correlated to differences in ICC Ca2+<\/jats:sup> signalling behaviours. Using ICC\u2010specific GCaMP6f mice we found that unlike the LES where only asynchronous Ca2+<\/jats:sup> transients were observed, two distinct ICC Ca2+<\/jats:sup> signalling behaviours were present within the distal oesophagus. Type I intramuscular interstitial cells of Cajal (ICC\u2010IM) exhibited localized asynchronous Ca2+<\/jats:sup> transients that were insensitive to ANO1 or voltage\u2010dependent Ca2+<\/jats:sup> channel (VDCC) inhibition but abolished by inhibiting endoplasmic reticulum (ER) Ca2+<\/jats:sup> release. In contrast type II ICC\u2010IM exhibited rhythmic, whole\u2010cell Ca2+<\/jats:sup> transients that were inhibited by ANO1 or VDCC antagonists revealing the underlying asynchronous Ca2+<\/jats:sup> release events. Phasic contractile activity in the mouse distal oesophagus was also inhibited by ANO1 and VDCC antagonists, suggesting a link between type II ICC\u2010IM Ca2+<\/jats:sup> signalling and contraction. mRNA encoding IP3<\/jats:sub>R1 and ANO1 channels was expressed in ICC\u2010IM. These data suggest that type II ICC\u2010IM are responsible for generating rhythmic, phasic activity in the distal oesophagus and that Ca2+<\/jats:sup> release occurs in ICC\u2010IM via IP3<\/jats:sub> receptors (IP3<\/jats:sub>Rs), which in turn activates ANO1, causing depolarization, Ca2+<\/jats:sup> influx via VDCCs and contraction.\nimage<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec>Key points<\/jats:title>\nThe oesophagogastric junction (EGJ) is a high\u2010pressure zone that prevents acid reflux into the oesophagus. Disrupted EGJ motility is associated with gastro\u2010oesophageal reflux disease or achalasia.<\/jats:p><\/jats:list-item>\nThe lower oesophageal sphincter (LES) generates tone, whereas the adjacent distal oesophagus exhibits phasic contractions. Both activities are dependent on anoctamin 1 (ANO1) and voltage\u2010dependent Ca2+<\/jats:sup> channels (VDCCs).<\/jats:p><\/jats:list-item>\nOnly intramuscular interstitial cells of Cajal (ICC\u2010IM) are present in the EGJ, yet two distinct ICC Ca2+<\/jats:sup> signalling behaviours were apparent. Type I ICC\u2010IM exhibited localized asynchronous Ca2+<\/jats:sup> transients, whereas type II ICC\u2010IM exhibited rhythmic whole\u2010cell Ca2+<\/jats:sup> transients that were inhibited by ANO1 and VDCC antagonists revealing the underlying asynchronous Ca2+<\/jats:sup> transients that were abolished\u00a0by IP3<\/jats:sub> receptor (IP3<\/jats:sub>R) inhibition.<\/jats:p><\/jats:list-item>\nmRNA encoding IP3<\/jats:sub>R1 and ANO1 was expressed in all ICC, suggesting that Ca2+<\/jats:sup> release via IP3<\/jats:sub>Rs leads to ANO1 activation, depolarization and subsequent Ca2+<\/jats:sup> influx via VDCCs.<\/jats:p><\/jats:list-item>\nType II ICC\u2010IM likely participate in generating pacemaker activity and regulating EGJ function.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1113\/jp288125","type":"journal-article","created":{"date-parts":[[2025,5,5]],"date-time":"2025-05-05T07:56:52Z","timestamp":1746431812000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A specialized population of intramuscular interstitial cells of Cajal regulates motility within the mouse oesophagogastric junction"],"prefix":"10.1113","author":[{"given":"Emer P.","family":"Ni Bhraonain","sequence":"first","affiliation":[{"name":"Department of Physiology and Cell Biology Reno School of Medicine, University of Nevada Reno Nevada USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0091-0640","authenticated-orcid":false,"given":"Karen I.","family":"Hannigan","sequence":"additional","affiliation":[{"name":"Department of Physiology and Cell Biology Reno School of Medicine, University 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