Calcium-induced transbilayer scrambling of fluorescent phospholipid analogs in platelets and erythrocytes

Abstract

The non-random distribution of phospholipids in the plasma membrane of human platelets and erythrocytes is at least partially maintained by the ATP-dependent aminophospholipid translocase, but can be disturbed by a calcium-induced scrambling of lipids. Using fluorescent NBD-phospholipid analogs, we demonstrate that in both cells the aminophospholipid translocase has a slightly higher preference for the naturally occurring l-isomer of the polar headgroup of phosphatidylserine as compared to the d-isomer. Calcium-induced outward movement of internalized phosphatidylserine probe, however, is not affected by the stereochemical configuration of the serine headgroup and is virtually identical to both the inward and outward movement of the phosphatidylcholine probe. The data also indicate that both in platelets and red blood cells the calcium-induced transbilayer movement is bidirectional and involves all major phospholipid classes, with reorientation rates of sphingomyelin being appreciably lower than that of the other phospholipid classes. While our results largely support earlier observations on red cells, they clearly differ from a recent study on platelets which suggested that calcium-induced scrambling is restricted to aminophospholipids and would not involve cholinephospholipids. The present results indicate that the same mechanism is responsible for calcium-induced lipid scrambling in red blood cells and platelets.