{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T10:14:59Z","timestamp":1773051299249,"version":"3.50.1"},"reference-count":52,"publisher":"Rockefeller University Press","issue":"1","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2004,7,1]]},"abstract":"<jats:p>Elevations of cytoplasmic free calcium concentrations ([Ca2+]i) evoked by cholinergic agonists stimulate isotonic fluid secretion in salivary acinar cells. This process is driven by the apical exit of Cl\u2212 through Ca2+-activated Cl\u2212 channels, while Cl\u2212 enters the cytoplasm against its electrochemical gradient via a loop diuretic-sensitive Na+-K+-2Cl\u2212 cotransporter (NKCC) and\/or parallel operations of Cl\u2212-HCO3\u2212 and Na+-H+ exchangers, located in the basolateral membrane. To characterize the contributions of those activities to net Cl\u2212 secretion, we analyzed carbachol (CCh)-activated Cl\u2212 currents in submandibular acinar cells using the \u201cgramicidin-perforated patch recording configuration.\u201d Since the linear polypeptide antibiotic gramicidin creates monovalent cation-selective pores, CCh-activated Cl\u2212 currents in the gramicidin-perforated patch recording were carried by Cl\u2212 efflux via Cl\u2212 channels, dependent upon Cl\u2212 entry through Cl\u2212 transporters expressed in the acinar cells. CCh-evoked oscillatory Cl\u2212 currents were associated with oscillations of membrane potential. Bumetanide, a loop diuretic, decreased the CCh-activated Cl\u2212 currents and hyperpolarized the membrane potential. In contrast, neither methazolamide, a carbonic anhydrase inhibitor, nor elimination of external HCO3\u2212 had significant effects, suggesting that the cotransporter rather than parallel operations of Cl\u2212-HCO3\u2212 and Na+-H+ exchangers is the primary Cl\u2212 uptake pathway. Pharmacological manipulation of the activities of the Ca2+-activated Cl\u2212 channel and the NKCC revealed that the NKCC plays a substantial role in determining the amplitude of oscillatory Cl\u2212 currents, while adjusting to the rate imposed by the Ca2+-activated Cl\u2212 channel, in the gramicidin-perforated patch configuration. By concerting with and being controlled by the cation steps, the oscillatory form of secretory Cl\u2212 movements may effectively provide a driving force for fluid secretion in intact acinar cells.<\/jats:p>","DOI":"10.1085\/jgp.200308948","type":"journal-article","created":{"date-parts":[[2004,6,28]],"date-time":"2004-06-28T21:58:06Z","timestamp":1088459886000},"page":"59-69","update-policy":"https:\/\/doi.org\/10.1085\/jgp.crossmarkpolicy","source":"Crossref","is-referenced-by-count":16,"title":["Gramicidin-perforated Patch Recording Revealed the Oscillatory Nature of Secretory Cl\u2212 Movements in Salivary Acinar Cells"],"prefix":"10.1085","volume":"124","author":[{"given":"Makoto","family":"Sugita","sequence":"first","affiliation":[{"name":"Department of Oral Physiology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8553, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chikara","family":"Hirono","sequence":"additional","affiliation":[{"name":"Department of Oral Physiology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8553, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshiki","family":"Shiba","sequence":"additional","affiliation":[{"name":"Department of Oral Physiology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8553, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"291","published-online":{"date-parts":[[2004,6,28]]},"reference":[{"key":"2023072520533016900_BIB1","doi-asserted-by":"crossref","first-page":"9868","DOI":"10.1021\/ja029317k","volume":"125","year":"2003","journal-title":"J. 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