{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:06:39Z","timestamp":1787015199114,"version":"build-2736575974"},"reference-count":44,"publisher":"Wiley","issue":"1-2","license":[{"start":{"date-parts":[[2006,5,22]],"date-time":"2006-05-22T00:00:00Z","timestamp":1148256000000},"content-version":"vor","delay-in-days":21,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Acta Physiologica"],"published-print":{"date-parts":[[2006,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:bold>Aim:\u2002<\/jats:bold>\n                    The role of high cholesterol\u2010containing microdomains in the signal transduction cascade leading to the activation of volume\u2010regulated anion channels (VRACs) was studied.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods:\u2002<\/jats:bold>\n                    Osmotic cell swelling\u2010induced efflux of\n                    <jats:sup>125<\/jats:sup>\n                    I\n                    <jats:sup>\u2212<\/jats:sup>\n                    was determined in human epithelial Intestine 407 cells and in skin fibroblasts obtained from healthy controls or Niemann\u2013Pick type C (NPC) patients. Cellular cholesterol content was modulated by pre\u2010incubation with 2\u2010hydroxypropyl\u2010\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \u2010cyclodextrin in the presence of acceptor lipid vesicles.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:\u2002<\/jats:bold>\n                    Osmotic cell swelling of human Intestine 407 cells leads to the rapid activation of a compensatory anion conductance. Treatment of the cells with cyclodextrin enhanced the response to submaximal hypotonic stimulation by approx. twofold, but did not further increase the efflux elicited by a saturating stimulus. In contrast, the volume\u2010sensitive anion efflux was markedly inhibited when cholesterol\u2010loaded cyclodextrin was used. Potentiation of the response by cholesterol depletion was maintained in caveolin\u20101 deficient Caco\u20102 colonocytes as well as in sphingomyelinase\u2010treated Intestine 407 cells, indicating that cholesterol\u2010rich microdomains are not crucially involved. However, treatment of the cells with progesterone, an inhibitor of NPC1\u2010dependent endosomal cholesterol trafficking, not only markedly reduced the hypotonicity\u2010provoked anion efflux, but also prevented its potentiation by cyclodextrin. In addition, the volume\u2010sensitive anion efflux from human NPC skin fibroblasts was significantly smaller when compared with control fibroblasts.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusions:\u2002<\/jats:bold>\n                    The results support a model of regulatory volume decrease involving recruitment of volume\u2010sensitive anion channels from intracellular compartments to the plasma membrane.\n                  <\/jats:p>","DOI":"10.1111\/j.1748-1716.2006.01534.x","type":"journal-article","created":{"date-parts":[[2006,5,22]],"date-time":"2006-05-22T06:12:03Z","timestamp":1148278323000},"page":"295-303","source":"Crossref","is-referenced-by-count":16,"title":["Regulation of the cell swelling\u2010activated chloride conductance by cholesterol\u2010rich membrane domains"],"prefix":"10.1111","volume":"187","author":[{"given":"C. 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