KCl cotransport mediates abnormal sulfhydryl-dependent volume regulation in sickle reticulocytes.

Blood
Clinton H JoinerRobert S Franco

Abstract

KCl cotransport (KCC) activation by cell swelling and pH was compared in sickle (SS) and normal (AA) red blood cells (RBCs). KCC fluxes had the same relationship to mean corpuscular hemoglobin concentration (MCHC) in SS and AA RBCs when normalized to the maximal volume-stimulated (VS(max)) flux (MCHC < 270 g/L [27 g/dL]). Acid-stimulated (pH 6.9) KCC flux in SS RBCs was 60% to 70% of VS(max) KCC versus 20% in AA RBCs. Density gradients were used to track changes in reticulocyte MCHC during KCC-mediated regulatory volume decrease (RVD). Swelling to MCHC of 260 g/L (26 g/dL) produced Cl-dependent RVD that resulted in higher MCHC in SS than AA reticulocytes. In acid pH, RVD was also greater in SS than AA reticulocytes. Sulfhydryl reduction by dithiothreitol (DTT) lowered VS(max) KCC flux in AA and SS RBCs by one third but did not alter swelling-induced RVD. DTT lowered acid-activated KCC in SS RBCs by 50% and diminished acid-induced RVD in SS reticulocytes. Thus, swelling activation of KCC is normal in SS RBCs but KCC-mediated RVD produces higher MCHC in SS than AA reticulocytes. Acid activation of KCC is exaggerated in SS RBCs and causes dehydration in SS reticulocytes. KCC response to acid stimulation was mitigated by DTT, sugge...Continue Reading

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Citations

Feb 8, 2006·The Journal of Membrane Biology·J E Capó-AponteP S Reinach
Dec 15, 2010·The Journal of Membrane Biology·Alina B ElperinDouglas B Light
Jul 8, 2011·The Journal of Biological Chemistry·Dao PanClinton H Joiner
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Nov 16, 2019·Pflügers Archiv : European journal of physiology·David C-Y LuJohn S Gibson
Apr 5, 2018·Clinical Hemorheology and Microcirculation·Carlo Brugnara

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