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To sustain the Cl<jats:sup>\u2212<\/jats:sup> secretion, [Cl<jats:sup>\u2212<\/jats:sup>]<jats:sub>i<\/jats:sub> must be maintained to levels that are greater than the electrochemical equilibrium mainly by Na<jats:sup>+<\/jats:sup>-K<jats:sup>+<\/jats:sup>-2Cl<jats:sup>\u2212<\/jats:sup> cotransporter-mediated Cl<jats:sup>\u2212<\/jats:sup> entry in basolateral membrane. Glucose transporters carry glucose into the cytoplasm, enabling the cells to produce ATP to maintain Cl<jats:sup>\u2212<\/jats:sup> and fluid secretion. Sodium\u2013glucose cotransporter-1 is a glucose transporter highly expressed in acinar cells. The salivary flow is suppressed by the sodium\u2013glucose cotransporter-1 inhibitor phlorizin. However, it remains elusive how sodium\u2013glucose cotransporter-1 contributes to maintaining salivary fluid secretion. To examine if sodium\u2013glucose cotransporter-1 activity is required for sustaining Cl<jats:sup>\u2212<\/jats:sup> secretion to drive fluid secretion, we analyzed the Cl<jats:sup>\u2212<\/jats:sup> currents activated by the cholinergic agonist, carbachol, in submandibular acinar cells while comparing the effect of phlorizin on the currents between the whole-cell patch and the gramicidin-perforated patch configurations. Phlorizin suppressed carbachol-induced oscillatory Cl<jats:sup>\u2212<\/jats:sup> currents by reducing the Cl<jats:sup>\u2212<\/jats:sup> efflux dependent on the Na<jats:sup>+<\/jats:sup>-K<jats:sup>+<\/jats:sup>-2Cl<jats:sup>\u2212<\/jats:sup> cotransporter-mediated Cl<jats:sup>\u2212<\/jats:sup> entry in addition to affecting TMEM16A activity. Our results suggest that the sodium\u2013glucose cotransporter-1 activity is necessary for maintaining the oscillatory Cl<jats:sup>\u2212<\/jats:sup> secretion supported by the Na<jats:sup>+<\/jats:sup>-K<jats:sup>+<\/jats:sup>-2Cl<jats:sup>\u2212<\/jats:sup> cotransporter activity in real time to drive fluid secretion. The concerted effort of sodium\u2013glucose cotransporter-1, Na<jats:sup>+<\/jats:sup>-K<jats:sup>+<\/jats:sup>-2Cl<jats:sup>\u2212<\/jats:sup> cotransporter, and apically located Cl<jats:sup>\u2212<\/jats:sup> channels might underlie the efficient driving of Cl<jats:sup>\u2212<\/jats:sup> secretion in different secretory epithelia from a variety of animal species.<\/jats:p>","DOI":"10.1007\/s00360-024-01532-w","type":"journal-article","created":{"date-parts":[[2024,2,3]],"date-time":"2024-02-03T06:02:21Z","timestamp":1706940141000},"page":"21-32","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Involvement of sodium\u2013glucose cotransporter-1 activities in maintaining oscillatory Cl\u2212 currents from mouse submandibular acinar cells"],"prefix":"10.1007","volume":"194","author":[{"given":"Misa","family":"Takeyasu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0235-6428","authenticated-orcid":false,"given":"Katsuyuki","family":"Kozai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3157-300X","authenticated-orcid":false,"given":"Makoto","family":"Sugita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,2,3]]},"reference":[{"key":"1532_CR1","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1016\/j.cbpa.2011.07.008","volume":"160","author":"LS Babonis","year":"2011","unstructured":"Babonis LS, Evans DH (2011) Morphological and biochemical evidence for the evolution of salt glands in snakes. 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