{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T21:46:37Z","timestamp":1767908797074,"version":"3.49.0"},"reference-count":51,"publisher":"Canadian Science Publishing","issue":"6","license":[{"start":{"date-parts":[[2006,12,1]],"date-time":"2006-12-01T00:00:00Z","timestamp":1164931200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.nrcresearchpress.com\/page\/about\/CorporateTextAndDataMining"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biochem. Cell Biol."],"published-print":{"date-parts":[[2006,12]]},"abstract":"<jats:p> Red blood cells (RBCs) possess the K\u2013Cl cotransport (KCC) isoforms 1, 3, and 4. Mutations within a given isoform may affect overall KCC activity. In a double-blind study, we analyzed, with Rb as a K congener, K fluxes (total flux, ouabain-sensitive Na<jats:sup>+<\/jats:sup>\/K<jats:sup>+<\/jats:sup> pump, and bumetanide-sensitive Na\u2013K\u20132Cl cotransport, Cl-dependent, and ouabain- and bumetanide-insensitive KCC\u00a0with or without stimulation by N-ethylmaleimide (NEM) and staurosporine or Mg removal, and basal channel-mediated fluxes, osmotic fragility, and ions and water in the RBCs of 8 controls, and of 8 patients with hereditary motor and sensory neuropathy with agenesis of corpus callosum (HMSN\u2013ACC) with defined KCC3 mutations (813FsX813 and Phe529FsX532) involving the truncations of 338 and 619 C-terminal amino acids, respectively. Water and ion content and, with one exception, mean osmotic fragility, as well as K fluxes without stimulating agents, were similar in controls and HMSN\u2013ACC RBCs. However, the NEM-stimulated KCC was reduced 5-fold (p\u00a0&lt; 0.0005) in HMSN\u2013ACC vs control RBCs, as a result of a lower V<jats:sub>max<\/jats:sub> (p\u00a0&lt; 0.05) rather than a lower K<jats:sub>m<\/jats:sub> (p = 0.109), accompanied by corresponding differences in Cl activation. Low intracellular Mg activated KCC in 6 out of 7 controls vs 1 out of 6 HMSN\u2013ACC RBCs, suggesting that regulation is compromised. The lack of differences in staurosporine-activated KCC indicates different action mechanisms. Thus, in HMSN\u2013ACC patients with KCC3 mutants, RBC KCC activity, although indistinguishable from that of the control group, responded differently to biochemical stressors, such as thiol alkylation or Mg removal, thereby indirectly indicating an important contribution of KCC3 to overall KCC function and regulation. <\/jats:p>","DOI":"10.1139\/o06-203","type":"journal-article","created":{"date-parts":[[2008,10,7]],"date-time":"2008-10-07T12:11:01Z","timestamp":1223381461000},"page":"1034-1044","source":"Crossref","is-referenced-by-count":9,"title":["K\u2013Cl cotransport in red blood cells from patients with KCC3 isoform mutantsThis paper is one of a selection of papers published in this Special Issue, entitled CSBMCB \u2014 Membrane Proteins in Health and Disease."],"prefix":"10.1139","volume":"84","author":[{"given":"P.K.","family":"Lauf","sequence":"first","affiliation":[{"name":"Cell Biophysics Group, Department of Pathology, Wright State University, Boonshoft School of Medicine, 3640 Col Glenn Hwy, Dayton, OH 45435, USA."},{"name":"Cell Biophysics Group, Department of Pharmacology and Toxicology, Wright State University Boonshoft School of Medicine, Dayton, OH, 45435 USA."},{"name":"Faculty of Medicine, Laval University, Qu\u00e9bec City, QC, G1K 7P4Canada"},{"name":"Center for Study of Brain Research, CHUM Research Center, University of Montreal, Montr\u00e9al, QC, H3C 3J7Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N.C.","family":"Adragna","sequence":"additional","affiliation":[{"name":"Cell Biophysics Group, Department of Pathology, Wright State University, Boonshoft School of Medicine, 3640 Col Glenn Hwy, Dayton, OH 45435, USA."},{"name":"Cell Biophysics Group, Department of Pharmacology and Toxicology, Wright State University Boonshoft School of Medicine, Dayton, OH, 45435 USA."},{"name":"Faculty of Medicine, Laval University, Qu\u00e9bec City, QC, G1K 7P4Canada"},{"name":"Center for Study of Brain Research, CHUM Research Center, University of Montreal, Montr\u00e9al, QC, H3C 3J7Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N.","family":"Dupre","sequence":"additional","affiliation":[{"name":"Cell Biophysics Group, Department of Pathology, Wright State University, Boonshoft School of Medicine, 3640 Col Glenn Hwy, Dayton, OH 45435, USA."},{"name":"Cell Biophysics Group, Department of Pharmacology and Toxicology, Wright State University Boonshoft School of Medicine, Dayton, OH, 45435 USA."},{"name":"Faculty of Medicine, Laval University, Qu\u00e9bec City, QC, G1K 7P4Canada"},{"name":"Center for Study of Brain Research, CHUM Research Center, University of Montreal, Montr\u00e9al, QC, H3C 3J7Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.P.","family":"Bouchard","sequence":"additional","affiliation":[{"name":"Cell Biophysics Group, Department of Pathology, Wright State University, Boonshoft School of Medicine, 3640 Col Glenn Hwy, Dayton, OH 45435, USA."},{"name":"Cell Biophysics Group, Department of Pharmacology and Toxicology, Wright State University Boonshoft School of Medicine, Dayton, OH, 45435 USA."},{"name":"Faculty of Medicine, Laval University, Qu\u00e9bec City, QC, G1K 7P4Canada"},{"name":"Center for Study of Brain Research, CHUM Research Center, University of Montreal, Montr\u00e9al, QC, H3C 3J7Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G.A.","family":"Rouleau","sequence":"additional","affiliation":[{"name":"Cell Biophysics Group, Department of Pathology, Wright State University, Boonshoft School of Medicine, 3640 Col Glenn Hwy, Dayton, OH 45435, USA."},{"name":"Cell Biophysics Group, Department of Pharmacology and Toxicology, Wright State University Boonshoft School of Medicine, Dayton, OH, 45435 USA."},{"name":"Faculty of Medicine, Laval University, Qu\u00e9bec City, QC, G1K 7P4Canada"},{"name":"Center for Study of Brain Research, CHUM Research Center, University of Montreal, Montr\u00e9al, QC, H3C 3J7Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"155","reference":[{"key":"atypb1\/ref1","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1007\/0-387-23752-6_35","volume":"559","author":"Adragna N.","year":"2004","journal-title":"Adv. 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