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Current models are largely based on experimental observations in enzymatically isolated cells where the Ca\n                    <jats:sup>2+<\/jats:sup>\n                    signal invariably propagates globally and thus appears ideally suited to activate spatially separated Cl and K channels, present on the apical and basolateral plasma membrane, respectively. We monitored Ca\n                    <jats:sup>2+<\/jats:sup>\n                    signals and salivary secretion in live mice expressing GCamp6F, following stimulation of the nerves innervating the submandibular gland. Consistent with in vitro studies, Ca\n                    <jats:sup>2+<\/jats:sup>\n                    signals were initiated in the apical endoplasmic reticulum. In marked contrast to in vitro data, highly localized trains of Ca\n                    <jats:sup>2+<\/jats:sup>\n                    transients that failed to fully propagate from the apical region were observed. Following stimuli optimum for secretion, large apical-basal gradients were elicited. A new mathematical model, incorporating these data was constructed to probe how salivary secretion can be optimally stimulated by apical Ca\n                    <jats:sup>2+<\/jats:sup>\n                    signals.\n                  <\/jats:p>","DOI":"10.7554\/elife.66170","type":"journal-article","created":{"date-parts":[[2021,7,9]],"date-time":"2021-07-09T08:00:45Z","timestamp":1625817645000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.66170","source":"Crossref","is-referenced-by-count":34,"title":["Highly localized intracellular Ca2+ signals promote optimal salivary gland fluid secretion"],"prefix":"10.7554","volume":"10","author":[{"given":"Takahiro","family":"Takano","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Physiology, University of Rochester, Rochester, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda M","family":"Wahl","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology, University of Rochester, Rochester, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai-Ting","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology, University of Rochester, Rochester, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0295-5014","authenticated-orcid":true,"given":"Takanori","family":"Narita","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, College of Bioresource Sciences, Nihon University, Fujisawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8009-4152","authenticated-orcid":true,"given":"John","family":"Rugis","sequence":"additional","affiliation":[{"name":"Department of Mathematics, University of Auckland, Auckland, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Sneyd","sequence":"additional","affiliation":[{"name":"Department of Mathematics, University of Auckland, Auckland, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6743-0668","authenticated-orcid":true,"given":"David I","family":"Yule","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology, University of Rochester, Rochester, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2021,7,9]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1085\/jgp.201110718","article-title":"Apical Ca2+-activated potassium channels in mouse parotid acinar cells","volume":"139","author":"Almassy","year":"2012","journal-title":"Journal of General Physiology"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1007\/s00424-018-2109-0","article-title":"New saliva secretion model based on the expression of Na+-K+ pump and K+ channels in the apical membrane of parotid acinar cells","volume":"470","author":"Alm\u00e1ssy","year":"2018","journal-title":"Pfl\u00fcgers Archiv - 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