{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T17:06:35Z","timestamp":1791047195457,"version":"4.1.0"},"reference-count":31,"publisher":"American Physiological Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Gastrointestinal and Liver Physiology"],"published-print":{"date-parts":[[2005,4]]},"abstract":"<jats:p>To investigate the interaction between the ion channels and transporters in the salivary fluid secretion, we measured the membrane voltage ( V<jats:sub>m<\/jats:sub>) and intracellular concentrations of Ca<jats:sup>2+<\/jats:sup>, Na<jats:sup>+<\/jats:sup>([Na<jats:sup>+<\/jats:sup>]<jats:sub>c<\/jats:sub>), Cl<jats:sup>\u2212<\/jats:sup>, and H<jats:sup>+<\/jats:sup>(pH<jats:sub>i<\/jats:sub>) in rat submandibular gland acini (RSMGA). After a transient depolarization induced by a short application of acetylcholine (ACh; 5 \u03bcM, 20 s), RSMGA showed strong delayed hyperpolarization ( V<jats:sub>h,ACh<\/jats:sub>; \u221295 \u00b1 1.8 mV) that was abolished by ouabain. In the HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup>-free condition, the V<jats:sub>h,ACh<\/jats:sub>was also blocked by bumetanide, a blocker of Na<jats:sup>+<\/jats:sup>-K<jats:sup>+<\/jats:sup>-2Cl<jats:sup>\u2212<\/jats:sup>cotransporter (NKCC). In the presence of HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup>(24 meq, bubbled with 5% CO<jats:sub>2<\/jats:sub>), however, the V<jats:sub>h,ACh<\/jats:sub>was not blocked by bumetanide, but it was suppressed by ethylisopropylamiloride (EIPA), a Na<jats:sup>+<\/jats:sup>\/H<jats:sup>+<\/jats:sup>exchanger (NHE) inhibitor. Similarly, the ACh-induced increase in [Na<jats:sup>+<\/jats:sup>]<jats:sub>c<\/jats:sub>was totally blocked by bumetanide in the absence of HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup>, but only by one-half in the presence of HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup>. ACh induced a prominent acidification of pH<jats:sub>i<\/jats:sub>in the presence of HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup>, and the acidification was further increased by EIPA treatment. Without HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup>, an application of ACh strongly accelerated the NKCC activity that was measured from the decay of pH<jats:sub>i<\/jats:sub>during the application of NH<jats:sub>4<\/jats:sub><jats:sup>+<\/jats:sup>(20 mM). Notably, the ACh-induced activation of NKCC was largely suppressed in the presence of HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup>. In summary, the ACh-induced anion secretion in RSMGA is followed by the activation of NKCC and NHE, resulting an increase in [Na<jats:sup>+<\/jats:sup>]<jats:sub>c<\/jats:sub>. The intracellular Na<jats:sup>+<\/jats:sup>-induced activation of electrogenic Na<jats:sup>+<\/jats:sup>\/K<jats:sup>+<\/jats:sup>-ATPase causes V<jats:sub>h,ACh<\/jats:sub>. The regulation of NKCC and NHE by ACh is strongly affected by the physiological level of HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup>.<\/jats:p>","DOI":"10.1152\/ajpgi.00406.2004","type":"journal-article","created":{"date-parts":[[2004,11,12]],"date-time":"2004-11-12T01:14:34Z","timestamp":1100222074000},"page":"G822-G831","source":"Crossref","is-referenced-by-count":6,"title":["Muscarinic activation of Na<sup>+<\/sup>-dependent ion transporters and modulation by bicarbonate in rat submandibular gland acinus"],"prefix":"10.1152","volume":"288","author":[{"given":"Ji Eun","family":"Lee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joo Hyun","family":"Nam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung Joon","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ph.47.030185.002553"},{"key":"R2","unstructured":"Cook DI, van Lennep EW, Roberts ML, and Young JA.Secretion by the major salivary glands. In:Physiology of the Gastrointestinal Tract(3rd ed.), edited by Johnson LR. New York: Raven, 1994."},{"key":"R3","unstructured":"Demaurex Nand Grinstein S.Na+\/H+antiport: modulation by ATP and role in cell volume regulation.J Exp Biol196: 389\u2013404, 1994."},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.1990.259.6.G1044"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M301899200"},{"key":"R6","doi-asserted-by":"crossref","unstructured":"Evans RL, Park K, Turner RJ, Watson GE, Nguyen HV, Dennett MR, Hand AR, Flagella M, Shull GE, and Melvin JE.Severe impairment of salivation in Na+\/K+\/2Cl\u2212cotransporter (NKCC1)-deficient mice.J Biol Chem275: 26720\u201326726, 2000.","DOI":"10.1016\/S0021-9258(19)61435-3"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1997.sp021932"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1023\/A:1006878324913"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2001.013453"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.62.1.515"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(03)00632-6"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1998.341bb.x"},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.1007\/BF01871782"},{"key":"R14","unstructured":"Manganel Mand Turner RJ.Rapid secretagogue-induced activation of Na+\/H+exchange in rat parotid acinar cells: possible interrelationship between volume regulation and stimulus secretion coupling.J Biol Chem266: 10182\u201310188, 1991."},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.1985.249.4.G464"},{"key":"R16","doi-asserted-by":"crossref","unstructured":"Melvin JE, Moran A, and Turner RJ.The role of HCO3\u2212and Na+\/H+exchange in the response of rat parotid acinar cells to muscarinic stimulation.J Biol Chem263: 19564\u201319569, 1988.","DOI":"10.1016\/S0021-9258(19)77673-X"},{"key":"R17","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.1992.263.6.G823"},{"key":"R18","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00044.2002"},{"key":"R19","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2000.t01-2-00139.x"},{"key":"R20","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00158.2003"},{"key":"R21","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.1999.276.2.G470"},{"key":"R22","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115695"},{"key":"R23","doi-asserted-by":"publisher","DOI":"10.1007\/BF00581349"},{"key":"R24","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.42.092001.143801"},{"key":"R25","doi-asserted-by":"publisher","DOI":"10.1007\/BF00581579"},{"key":"R26","unstructured":"Robertson MAand Foskett JK.Na+transport pathways in secretory acinar cells: membrane cross talk mediated by [Cl\u2212]i.Am J Physiol Cell Physiol267: C146\u2013C156, 1994."},{"key":"R27","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.1.287"},{"key":"R28","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M400639200"},{"key":"R29","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.2000.279.3.C541"},{"key":"R30","doi-asserted-by":"publisher","DOI":"10.1034\/j.1601-0825.2002.10815.x"},{"key":"R31","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1993.264.1.C54"}],"container-title":["American Journal of Physiology-Gastrointestinal and Liver Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajpgi.00406.2004","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,6,28]],"date-time":"2021-06-28T05:44:26Z","timestamp":1624859066000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajpgi.00406.2004"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,4]]},"references-count":31,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2005,4]]}},"alternative-id":["10.1152\/ajpgi.00406.2004"],"URL":"https:\/\/doi.org\/10.1152\/ajpgi.00406.2004","relation":{},"ISSN":["0193-1857","1522-1547"],"issn-type":[{"value":"0193-1857","type":"print"},{"value":"1522-1547","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,4]]}}}