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The present study was performed in pursuit of effective modulators of ATP release under physiologic conditions in polarized human airway epithelial cells (Calu-3). Neither isoproterenol, forskolin, nor ionomycin augmented extracellular ATP release detected by luciferase assay. However, direct activation of the human intermediate conductance, Ca2+-activated K+ channel (hIK-1) by 1-ethyl-2-benzimdazolinone (1-EBIO, 1 mM) and chlorzoxazone (CZ, 1 mM) increased ATP release predominantly in the apical compartment. Measurement of fluo-3 signals revealed that 1-EBIO\u2013 and CZ-stimulated cytosolic Ca2+ mobilization was suppressed by the presence of MRS-2179, a specific P2Y1 receptor antagonist. The hIK-1\u2013mediated ATP release was inhibited by a hIK-1 blocker (charybdotoxin), and an Na+-K+-2Cl\u2212 cotransport blocker (bumetanide) without interruption by GdCl3, an inhibitor of stretch-activated nonselective cation (SA) channels, or glybenclamide, a blocker of the cystic fibrosis transmembrane conductance regulator (CFTR). These results suggest that a cell volume decrease via the hIK-1\u2013mediated KCl loss and the resultant induction of a regulatory volume increase via the Na+-K+-2Cl\u2212 transporter may trigger release of ATP, which causes P2Y1-mediated Ca2+ mobilization, through mechanisms unrelated to the CFTR and SA channels.<\/jats:p>","DOI":"10.1165\/rcmb.2003-0184oc","type":"journal-article","created":{"date-parts":[[2003,9,1]],"date-time":"2003-09-01T20:41:47Z","timestamp":1062448907000},"page":"388-395","source":"Crossref","is-referenced-by-count":28,"title":["ATP Release Triggered by Activation of the Ca2+-Activated K+ Channel in Human Airway Calu-3 Cells"],"prefix":"10.1093","volume":"30","author":[{"given":"Yasushi","family":"Ito","sequence":"first","affiliation":[{"name":"Division of Respiratory Diseases, Department of Internal Medicine, and Department of Cellular Physiology, Nagoya University Graduate School of Medicine, Nagoya, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masami","family":"Son","sequence":"additional","affiliation":[{"name":"Division of Respiratory Diseases, Department of Internal Medicine, and Department of Cellular Physiology, Nagoya University Graduate School of Medicine, Nagoya, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinji","family":"Sato","sequence":"additional","affiliation":[{"name":"Division of Respiratory Diseases, Department of Internal Medicine, and Department of Cellular Physiology, Nagoya University Graduate School of Medicine, Nagoya, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takayuki","family":"Ishikawa","sequence":"additional","affiliation":[{"name":"Division of Respiratory Diseases, Department of Internal Medicine, and Department of Cellular Physiology, Nagoya University Graduate School of Medicine, Nagoya, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masashi","family":"Kondo","sequence":"additional","affiliation":[{"name":"Division of Respiratory Diseases, Department of Internal Medicine, and Department of Cellular Physiology, Nagoya University Graduate School of Medicine, Nagoya, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinsuke","family":"Nakayama","sequence":"additional","affiliation":[{"name":"Division of Respiratory Diseases, Department of Internal Medicine, and Department of Cellular Physiology, Nagoya University Graduate School of Medicine, Nagoya, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaoru","family":"Shimokata","sequence":"additional","affiliation":[{"name":"Division of Respiratory Diseases, Department of Internal Medicine, and Department of Cellular Physiology, Nagoya University Graduate School of Medicine, Nagoya, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroaki","family":"Kume","sequence":"additional","affiliation":[{"name":"Division of Respiratory Diseases, Department of Internal Medicine, and Department of Cellular Physiology, Nagoya University Graduate School of Medicine, Nagoya, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2004,3,1]]},"reference":[{"key":"2026030623492510600_BIB1","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/S0031-6997(24)01373-5","volume":"50","year":"1998","journal-title":"Pharmacol. 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