Failure of phosphatidic acid to translocate Ca²⁺ across phosphatidylcholine membranes

Abstract

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 cells¹. The ionophoretic properties of PA are evident in its ability to translocate Ca²⁺ across a layer of organic solvent². When added exogenously to some cells, PA produces a physiological response^3–6 and in neuroblastoma cells stimulation of Ca²⁺ uptake can also be detected⁶. 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.