{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:46:48Z","timestamp":1787017608151,"version":"build-2736575974"},"reference-count":105,"publisher":"American Physiological Society","issue":"4","funder":[{"name":"Dayton Children's Hospital Foundation","award":["15-425-1\/15-0395"],"award-info":[{"award-number":["15-425-1\/15-0395"]}]},{"name":"Wright State University, Boonshoft School of Medicine, Seed-Grant-Proteomics Program","award":["229117 RIF"],"award-info":[{"award-number":["229117 RIF"]}]},{"DOI":"10.13039\/100000065","name":"HHS | NIH | National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["NS29227"],"award-info":[{"award-number":["NS29227"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000082","name":"NSF | EHR | Division of Graduate Education","doi-asserted-by":"publisher","award":["DGE-0504438"],"award-info":[{"award-number":["DGE-0504438"]}],"id":[{"id":"10.13039\/100000082","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2019,4,1]]},"abstract":"<jats:p>\n                    Choroid plexus epithelial cells (CPECs) secrete cerebrospinal fluid (CSF). They express Na\n                    <jats:sup>+<\/jats:sup>\n                    -K\n                    <jats:sup>+<\/jats:sup>\n                    -ATPase and Na\n                    <jats:sup>+<\/jats:sup>\n                    -K\n                    <jats:sup>+<\/jats:sup>\n                    -2Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    cotransporter 1 (NKCC1) on their apical membrane, deviating from typical basolateral membrane location in secretory epithelia. Given this peculiarity, the direction of basal net ion fluxes mediated by NKCC1 in CPECs is controversial, and cotransporter function is unclear. Determining the direction of basal NKCC1-mediated fluxes is critical to understanding the function of apical NKCC1. If NKCC1 works in the net efflux mode, it may be directly involved in CSF secretion. Conversely, if NKCC1 works in the net influx mode, it would have an absorptive function, contributing to intracellular Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    concentration ([Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    ]\n                    <jats:sub>i<\/jats:sub>\n                    ) and cell water volume (CWV) maintenance needed for CSF secretion. We resolve this long-standing debate by electron microscopy (EM), live-cell-imaging microscopy (LCIM), and intracellular Na\n                    <jats:sup>+<\/jats:sup>\n                    and Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    measurements in single CPECs of NKCC1+\/+ and NKCC1\u2212\/\u2212 mouse. NKCC1-mediated ion and associated water fluxes are tightly linked, thus their direction is inferred by measuring CWV changes. Genetic or pharmacological NKCC1 inactivation produces CPEC shrinkage. EM of NKCC1\u2212\/\u2212 CPECs in situ shows they are shrunken, forming large dilations of their basolateral extracellular spaces, yet remaining attached by tight junctions. Normarski LCIM shows in vitro CPECs from NKCC1\u2212\/\u2212 are ~17% smaller than NKCC1+\/+. CWV measurements in calcein-loaded CPECs show that bumetanide (10 \u03bcM) produces ~16% decrease in CWV in NKCC1+\/+ but not in NKCC1\u2212\/\u2212 CPECs. Our findings suggest that under basal conditions apical NKCC1 is continuously active and works in the net inward flux mode maintaining [Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    ]\n                    <jats:sub>i<\/jats:sub>\n                    and CWV needed for CSF secretion.\n                  <\/jats:p>","DOI":"10.1152\/ajpcell.00026.2018","type":"journal-article","created":{"date-parts":[[2018,12,21]],"date-time":"2018-12-21T15:56:16Z","timestamp":1545407776000},"page":"C525-C544","source":"Crossref","is-referenced-by-count":67,"title":["Genetic and pharmacological inactivation of apical Na\n                    <sup>+<\/sup>\n                    -K\n                    <sup>+<\/sup>\n                    -2Cl\n                    <sup>\u2212<\/sup>\n                    cotransporter 1 in choroid plexus epithelial cells reveals the physiological function of the cotransporter"],"prefix":"10.1152","volume":"316","author":[{"given":"Jeannine M. 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