Distribution of plasma membrane Ca2+ pump activity in normal human red blood cells

The plasma membrane calcium pump (PMCA) is the only active Ca2+ transporter in human red blood cells (RBCs). Previous measurements of maximal Ca2+ extrusion rates (V-max) reported only mean values in the RBC population. Despite early evidence for differences in Ca2+ extrusion capacity among RBCs, the precise V-max distribution remained unknown. It was important to characterize this distribution to assess the range and modality (uni- or multimodal) of PMCA V-max variation and the likelihood of RBCs with elevated [Ca2+](i) in the circulation participating in physiologic and pathologic processes. We report here the application of a new method to investigate the detailed distribution of PMCA V-max activity in RBCs. The migrating profile of osmotic lysis curves was used to identify and quantity the fraction of cells that extrude a uniform Ca2+ load at different rates. The results revealed that RBCs from single donors have large variations in PMCA activity that follow a unimodal, broad distribution pattern consistently skewed toward higher V-max values, suggesting an excess of cells with V-max higher than the mean value. The method applied may provide a way of evaluating whether the observed variation in PMCA V-max is related to cell age. (C) 2003 by The American Society of Hematology.