Alteration of red blood cell (RBC) pH produces stomatocytosis (at low
pH) and echinocytosis (at high pH). Cell shrinkage potentiates high pH
echinocytosis, but shrinkage alone does not cause echinocytosis. Mech
anisms for these shape changes have not been described. In this study,
measured dependence of RBC shape on cell pH was nonlinear, with a bro
ad pH range in which normal discoid shape was maintained. Transbilayer
distribution of phosphatidylcholine and phosphatidylserine, measured
by back-extraction of radiolabeled lipid, was the same in control and
altered pH cells. Possible roles of pH-titratable inner monolayer phos
pholipids were examined by assessing pH-dependent shape in cells in wh
ich their levels had been perturbed. In metabolically depleted cells a
nd calcium-treated cells, which have altered levels of phosphatidic ac
id, phosphatidylinositol-4-phosphate, and/or phosphatidylinositol-4,5-
bisphosphate, low cell pH was stomatocytogenic and high cell pH was ec
hinocytogenic, as in control cells. Thus, neither change in membrane l
ipid asymmetry nor normal levels of the pH-titratable inner monolayer
lipids is necessary for cell pH-mediated shape change. (C) 1995 by The
American Society of Hematology.