{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T02:09:58Z","timestamp":1747188598757,"version":"3.40.5"},"reference-count":39,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,11,23]],"date-time":"2018-11-23T00:00:00Z","timestamp":1542931200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP26462821","JP17K11651","JP16K11484"],"award-info":[{"award-number":["JP26462821","JP17K11651","JP16K11484"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["JP16H01433"],"award-info":[{"award-number":["JP16H01433"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Physiology"],"published-print":{"date-parts":[[2019,1]]},"abstract":"<jats:sec><jats:title>New Findings<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p><jats:bold>What is the central question of this study?<\/jats:bold><\/jats:p>\n<jats:p>The effects of Ca<jats:sup>2+<\/jats:sup> responses on salivary fluid secretion have been studied indirectly by monitoring ion channel activities and other indices. Therefore, Ca<jats:sup>2+<\/jats:sup> responses during salivary secretion remain poorly understood.<\/jats:p>\n<\/jats:list-item>\n<jats:list-item><jats:p><jats:bold>What is the main finding and its importance?<\/jats:bold><\/jats:p>\n<jats:p>Herein, we developed a simultaneous monitoring system for Ca<jats:sup>2+<\/jats:sup> responses and salivary secretion in live animals using a YC\u2010Nano50\u2010expressing submandibular gland and a fibre\u2010optic pressure sensor. This new approach revealed a clear time lag between the onset of Ca<jats:sup>2+<\/jats:sup> responses and salivary secretion. We also estimated the [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> and provided direct evidence for the regulation of salivary secretion by small increases in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> in submandibular gland acinar cells.<\/jats:p>\n<\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>We monitored changes in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> during salivary secretion in the rat submandibular gland in live animals using a combination of intravital Ca<jats:sup>2+<\/jats:sup> imaging with the ultrasensitive Ca<jats:sup>2+<\/jats:sup> indicator YC\u2010Nano50 and a fibre\u2010optic pressure sensor. Intravenous infusion of ACh (10\u2013720\u00a0nmol\u00a0min<jats:sup>\u22121<\/jats:sup>) increased [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> and salivary flow rate in a dose\u2010dependent manner. Repetitive stimulation with ACh induced equivalent Ca<jats:sup>2+<\/jats:sup> responses and salivary secretion in the same individual animals. The accurate ACh stimulation experiments revealed a clear time lag between the onset of the increase in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> and salivary secretion. The time lag with the lowest dose of ACh (30\u00a0nmol\u00a0min<jats:sup>\u22121<\/jats:sup>) was 106 s, which shortened to 19 s with the dose used for maximal salivary secretion (360\u00a0nmol\u00a0min<jats:sup>\u22121<\/jats:sup>). This time lag might reflect the time required for [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> to reach the level required to activate molecules for fluid secretion. The resting [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> in submandibular gland was 37\u00a0n<jats:sc>m<\/jats:sc>, and [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> at the onset of salivary secretion was 45\u201357\u00a0n<jats:sc>m<\/jats:sc>, irrespective of ACh dose. These results indicate that low [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> is sufficient to trigger fluid secretion in the rat submandibular gland <jats:italic>in vivo<\/jats:italic>.<\/jats:p><\/jats:sec>","DOI":"10.1113\/ep086868","type":"journal-article","created":{"date-parts":[[2018,10,27]],"date-time":"2018-10-27T14:54:51Z","timestamp":1540652091000},"page":"61-69","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Simultaneous monitoring of Ca<sup>2+<\/sup> responses and salivary secretion in live animals reveals a threshold intracellular Ca<sup>2+<\/sup> concentration for salivation"],"prefix":"10.1113","volume":"104","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7130-4912","authenticated-orcid":false,"given":"Akihiro","family":"Nezu","sequence":"first","affiliation":[{"name":"Department of Pharmacology School of Dentistry Health Sciences University of Hokkaido  Ishikari\u2010Tobetsu Hokkaido 061\u20100293 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takao","family":"Morita","sequence":"additional","affiliation":[{"name":"Department of Biochemistry The Nippon Dental University School of Life Dentistry at Niigata  1\u20138 Hamaura\u2010cho Chuo\u2010ku Niigata 951\u20108580 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takeharu","family":"Nagai","sequence":"additional","affiliation":[{"name":"Institute of Scientific and Industrial Research Osaka University  8\u20101 Mihogaoka Ibaraki Osaka 567\u20100047 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akihiko","family":"Tanimura","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Dentistry Health Sciences University of Hokkaido  Ishikari\u2010Tobetsu Hokkaido 061\u20100293 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,11,23]]},"reference":[{"doi-asserted-by":"publisher","key":"e_1_2_7_2_1","DOI":"10.1016\/j.ceca.2014.02.009"},{"doi-asserted-by":"publisher","key":"e_1_2_7_3_1","DOI":"10.1172\/JCI105974"},{"key":"e_1_2_7_4_1","first-page":"89","article-title":"Sialorrhea: A review of a vexing, often unrecognized sign of oropharyngeal and esophageal disease","volume":"39","author":"Boyce H. 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