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In the current study, we sought to determine the ion transporters involved in Cl<jats:sup>-<\/jats:sup>secretion and whether secretion is regulated by PKA and glucocorticoids.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Short circuit current (<jats:italic>I<\/jats:italic><jats:sub><jats:italic>sc<\/jats:italic><\/jats:sub>) from rat SCCD epithelia demonstrated stimulation by forskolin (EC<jats:sub>50<\/jats:sub>: 0.8 \u03bcM), 8-Br-cAMP (EC<jats:sub>50<\/jats:sub>: 180 \u03bcM), 8-pCPT-cAMP (100 \u03bcM), IBMX (250 \u03bcM), and RO-20-1724 (100 \u03bcM). The PKA activator N6-BNZ-cAMP (0.1, 0.3 &amp; 1 mM) also stimulated<jats:italic>I<\/jats:italic><jats:sub><jats:italic>sc<\/jats:italic><\/jats:sub>. Partial inhibition of stimulated<jats:italic>I<\/jats:italic><jats:sub><jats:italic>sc<\/jats:italic><\/jats:sub>individually by bumetanide (10 &amp; 50 \u03bcM), and [(dihydroindenyl)oxy]alkanoic acid (DIOA, 100 \u03bcM) were additive and complete. Stimulated<jats:italic>I<\/jats:italic><jats:sub><jats:italic>sc<\/jats:italic><\/jats:sub>was also partially inhibited by CFTR<jats:sub>inh<\/jats:sub>-172 (5 &amp; 30 \u03bcM), flufenamic acid (5 \u03bcM) and diphenylamine-2,2<jats:sup>\u2032<\/jats:sup>-dicarboxylic acid (DPC; 1 mM). Native canals of CFTR<jats:sup>+\/\u2212<\/jats:sup>mice showed a stimulation of I<jats:sub>sc<\/jats:sub>from isoproterenol and forskolin+IBMX but not in the presence of both bumetanide and DIOA, while canals from CFTR<jats:sup>\u2212\/\u2212<\/jats:sup>mice had no responses. Nonetheless, CFTR<jats:sup>\u2212\/\u2212<\/jats:sup>mice showed no difference from CFTR<jats:sup>+\/\u2212<\/jats:sup>mice in their ability to balance (rota-rod). Stimulated<jats:italic>I<\/jats:italic><jats:sub><jats:italic>sc<\/jats:italic><\/jats:sub>was greater after chronic incubation (24 hr) with the glucocorticoids dexamethasone (0.1 &amp; 0.3 \u03bcM), prednisolone (0.3, 1 &amp; 3 \u03bcM), hydrocortisone (0.01, 0.1 &amp; 1 \u03bcM), and corticosterone (0.1 &amp; 1 \u03bcM) and mineralocorticoid aldosterone (1 \u03bcM). Steroid action was blocked by mifepristone but not by spironolactone, indicating all the steroids activated the glucocorticoid, but not mineralocorticoid, receptor. Expression of transcripts for CFTR; for KCC1, KCC3a, KCC3b and KCC4, but not KCC2; for NKCC1 but not NKCC2 and for WNK1 but only very low WNK4 was determined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These results are consistent with a model of Cl<jats:sup>-<\/jats:sup>secretion whereby Cl<jats:sup>-<\/jats:sup>is taken up across the basolateral membrane by a Na<jats:sup>+<\/jats:sup>-K<jats:sup>+<\/jats:sup>-2Cl<jats:sup>-<\/jats:sup>cotransporter (NKCC) and potentially another transporter, is secreted across the apical membrane via a Cl<jats:sup>-<\/jats:sup>channel, likely CFTR, and demonstrate the regulation of Cl<jats:sup>-<\/jats:sup>secretion by protein kinase A and glucocorticoids.<\/jats:p><\/jats:sec>","DOI":"10.1186\/1472-6793-13-6","type":"journal-article","created":{"date-parts":[[2013,3,27]],"date-time":"2013-03-27T21:21:42Z","timestamp":1364419302000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["cAMP-stimulated Cl- secretion is increased by glucocorticoids and inhibited by bumetanide in semicircular canal duct epithelium"],"prefix":"10.1186","volume":"13","author":[{"given":"Satyanarayana R","family":"Pondugula","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suresh B","family":"Kampalli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert C","family":"De Lisle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nithya N","family":"Raveendran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald G","family":"Harbidge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel C","family":"Marcus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2013,3,27]]},"reference":[{"key":"208_CR1","first-page":"649","volume-title":"Acoustic Transduction","author":"DC Marcus","year":"2012","unstructured":"Marcus DC, Acoustic Transduction: Acoustic Transduction. 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