Anemia Research Today is a free monthly online journal that collates and summarizes the latest research about Anemia, including details on symptoms, diagnosis, diet, treatment, causes.

Urea stimulation of KCl cotransport induces abnormal volume reduction in sickle reticulocytes.

Joiner CH, Rettig RK, Jiang M, Risinger M, Franco RS

Cincinnati Comprehensive Sickle Cell Center, Division of Hematology/Oncology, University of Cincinnati College of Medicine, and Department of Pediatrics, Cincinnati Children's Hospital Medical Center, OH 45229, USA. clinton.joiner@cchmc.org

KCl cotransport (KCC) activity contributes to pathologic dehydration in sickle (SS) red blood cells (RBCs). KCC activation by urea was measured in SS and normal (AA) RBCs as Cl-dependent Rb influx. KCC-mediated volume reduction was assessed by measuring reticulocyte cellular hemoglobin concentration (CHC) cytometrically. Urea activated KCC fluxes in fresh RBCs to levels seen in swollen cells, although SS RBCs required lower urea concentrations than did normal (AA) RBCs. Little additional KCC stimulation by urea occurred in swollen AA or SS RBCs. The pH dependence of KCC in "euvolemic" SS RBCs treated with urea was similar to that in swollen cells. Urea triggered volume reduction in SS and AA reticulocytes, establishing a higher CHC. Volume reduction was Cl dependent and was limited by the KCC inhibitor, dihydro-indenyl-oxyalkanoic acid. Final CHC depended on urea concentration, but not on initial CHC. Under all activation conditions, volume reduction was exaggerated in SS reticulocytes and produced higher CHCs than in AA reticulocytes. The sulfhydryl-reducing agent, dithiothreitol, normalized the sensitivity of KCC activation to urea in SS RBCs and mitigated the urea-stimulated volume decrease in SS reticulocytes, suggesting that the dysfunctional activity of KCC in SS RBCs was due in part to reversible sulfhydryl oxidation.

Published 7 February 2007 in Blood, 109(4): 1728-35.
Full-text of this article is available online (may require subscription).

© 2004-2008 Anemia Research Today. All Rights Reserved.