Actions of serum and plasma albumin on intracellular Ca2+ in human endothelial cells

1. The effects of serum and plasma albumin on [Ca2+](i) in human endothelial cells were examined using single-cell Ca2+ imaging. Two types of endothelial cell were used: human umbilical vein endothelial cells (HUVEC) in primary culture, and the endothelial-derived cell line ECV304. 2. Serum albumin caused a large and transient rise in [Ca2+](i), due to Ca2+ release from an IP3-sensitive internal store, followed by a maintained elevation in [Ca2+](i) attributable to Ca2+ influx from the external medium. A half-maximal rise in [Ca2+](i) was produced by a concentration of serum albumin of about 1 mu g ml(-1). 3. The Ca2+-releasing action of serum albumin is abolished by methanol extraction and is therefore attributable to an attached polar lipid. A possible candidate is lysophosphatidic acid, known to be released from platelets during blood coagulation, which produced similar effects to those of serum albumin: 4. In HUVEC, plasma albumin caused a sustained decrease in [Ca2+](i) from the mean resting level of 114 nar to 58 nM. No effect of plasma albumin was observed in ECV304 cells. 5. The decrease in [Ca2+](i) cansed by plasma albumin is due to an uptake into intracellular stores. The store loading substantially potentiates the action of Ca2+-releasing agonists such as histamine. 6. The results show that normal plasma albumin, which carries few lipids, lowers [Ca2+](i) and potentiates the actions of Ca2+-releasing agonists by promoting Ca2+ uptake into intracellular stores. When converted to the serum form, by binding lysophosphatidic acid released during blood coagulation, albumin has a potent effect in elevating [Ca2+](i). Blood coagulation may therefore play a role in regulating vascular tone and capillary permeability.