{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T16:18:13Z","timestamp":1770740293498,"version":"3.49.0"},"reference-count":28,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"published-print":{"date-parts":[[2002,5,1]]},"abstract":"<jats:p> In this study, we tested the hypothesis that intracellular Cl<jats:sup>\u2212<\/jats:sup>(Cl[Formula: see text]) regulates the activity of protein kinase C (PKC)-\u03b4 and thus the activation of Na-K-Cl cotransport (NKCC1) in a Calu-3 cell line. The \u03b1<jats:sub>1<\/jats:sub>-adrenergic agonist methoxamine (MOX) and hypertonic sucrose increased Cl[Formula: see text] and increased or decreased intracellular volume, respectively, without changing Cl[Formula: see text] concentration ([Cl<jats:sup>\u2212<\/jats:sup>]<jats:sub>i<\/jats:sub>). Titration of [Cl<jats:sup>\u2212<\/jats:sup>]<jats:sub>i<\/jats:sub> from 20\u2013140 mM in nystatin-permeabilized cell monolayers did not affect the baseline activity of PKC-\u03b4, PKC-\u03b6, or rottlerin-sensitive NKCC1. At 200 mM Cl<jats:sup>\u2212<\/jats:sup>, rottlerin-sensitive NKCC1 was activated, and PKC isotypes were localized predominantly to a particulate fraction. MOX induced a biphasic increase in NKCC1 activity and PKC-\u03b4 in activity and particulate localization of PKC-\u03b4 and -\u03b6. Activity of NKCC1 and PKC-\u03b4 decreased with increasing Cl[Formula: see text] from 20 to 80 mM Cl[Formula: see text] then increased at 140\u2013200 mM Cl[Formula: see text] apparently as an additive effect to high [Cl<jats:sup>\u2212<\/jats:sup>]<jats:sub>i<\/jats:sub> levels. Rottlerin inhibited the effects of MOX, which indicates that PKC-\u03b4 was required for activation of NKCC1. The results indicate that, in airway epithelial cells, a Cl[Formula: see text] electrochemical gradient alone is not sufficient to stimulate NKCC1 activity; rather, elevated activity of PKC-\u03b4 is necessary. Further, high Cl[Formula: see text] levels induce a subcellular redistribution of PKC-\u03b4, which results in increased enzyme activity. <\/jats:p>","DOI":"10.1152\/ajplung.00143.2001","type":"journal-article","created":{"date-parts":[[2015,3,3]],"date-time":"2015-03-03T15:16:48Z","timestamp":1425395808000},"page":"L1151-L1159","source":"Crossref","is-referenced-by-count":20,"title":["Modulation of Na-K-2Cl cotransport by intracellular Cl<sup>\u2212<\/sup>  and protein kinase C-\u03b4 in Calu-3 cells"],"prefix":"10.1152","volume":"282","author":[{"given":"Carole M.","family":"Liedtke","sequence":"first","affiliation":[{"name":"W. A. Bernbaum Center for Cystic Fibrosis Research, Departments of Pediatrics and Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44106-4948"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Papay","sequence":"additional","affiliation":[{"name":"W. A. 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