The Complex of Phosphatidylinositol 4,SBisphosphate and Calcium Ions Is Not Responsible for Ca2+-Induced Loss of Phospholipid Asymmetry in the Human Erythrocyte: A Study in Scott Syndrome, a Disorder of Calcium-Induced Phospholipid Scrambling

Elevation of cytoplasmic Ca2+ levels in human erythrocytes induces a progressive loss of membrane phospholipid asymmetry, a process that is impaired in erythrocytes from a patient with Scott syndrome. We show here that porcine erythrocytes are similarly incapable of Ca2'-induced redistribution of membrane phospholipids. Because a complex of phosphatidylinositol 4.5-bisphosphate (PIP,) and Ca2+ has been proposed as the mediator of enhanced transbilayer movement of lipids (J Biol Chem 269:6347,7994), these cell systems offer a unique opportunity for testing this mechanism. Analysis of both total PIP2 content and the metabolicresistant pool of PIP, that remains after incubation with Ca2+ ionophore showed no appreciable differences between normal and Scott erythrocytes. Moreover, porcine erythrocytes were found to have slightly higher levels of both total and metabolic-resistant PIP, in comparison with normal human erythrocytes. Although loading of normal erythrocytes with