Failure of phosphatidic acid to translocate Ca2+ across phosphatidylcholine membranes

The putative role of phosphatidic acid (PA) as a Ca2+ ionophore has offered an attractive explanation for the relationship between Ca2+ influx and the turnover of phosphoinositides in stimulated cells. The ionophoretic properties of PA are evident in its ability to translocate Ca2+ across a layer of organic solvent. When added exogenously to some cells, PA produces a physiological response and in neuroblastoma cells stimulation of Ca2+ uptake can also be detected. It was later shown that low levels of PA added exogenously to, or incorporated endogenously in liposomes, increase their permeability to Ca2+ (refs 7, 8), indicating a direct effect of PA on lipid bilayer properties. We now report, however, that we have not been able to demonstrate facilitation by PA of Ca2+ fluxes across liposomal membranes. Ascribing such a role to PA does not seem compatible with known features of biological membranes or the properties of ionophores known to translocate ions across membranes.