K+ transport in red blood cells from human umbilical cord

The current study was designed to characterise K+ transport in human fetal red blood cells, containing mainly haemoglobin F (HbF, and termed HbF cells ), isolated from umbilical cords following normal parturition. Na+/K+ pump activity was comparable to that in normal adult human red cells (which cont ain HbA, and are termed HbA cells). Passive (ouabain-resistant) K+ transpor t was dominated by a bumetanide (10 muM)-resistant component, inhibited by [(dihydroxyindenyl) oxy]alkanoic acid (100 muM), calyculin A (100 nM) and C l- removal, and stimulated by N-ethylmaleimide (1 mM) and staurosporine (2 muM)- all consistent with mediation via the K+-Cl- cotransporter (KCC). KCC activity in HbF cells was also O-2-dependent and stimulated by swelling an d urea, and showed a biphasic response to changes in external pH. Peak acti vity of KCC in HbF cells was about 3-fold that in HbA cells. These characte ristics are qualitatively similar to those observed in HbA cells, notwithst anding the different conditions experienced by HbF cells in vivo, and the p resence of HbF rather than HbA. KCC in HbF cells has a higher total capacit y, but when measured at the ambient PO2 of fetal blood it would be similar in magnitude to that in fully oxygenated HbA cells, and about that required to balance K+ accumulation via the Na+/K+ pump. These findings are relevan t to the mechanism by which O-2 regulates membrane transporters in red bloo d cells, and to the strategy of promoting HbF synthesis as a therapy for pa tients with sickle cell disease. (C) 2001 Elsevier Science B.V. All rights reserved.