Extrusion mechanisms of intracellular Ca2+ in human aortic endothelial cells.

Although participation of the plasma membrane Ca2+ pump in Ca2+ efflux has been generally accepted, the existence of Na(2+)-Ca2+ exchange in endothelial cells is still controversial. In the present experiments, the role of Na(+)-Ca2+ exchange and Ca(2+)-ATPase were examined in cultured human aortic endothelial cells loaded with fura. In Ca(2+)-free solution, the declining phase of [Ca2+]i in response to histamine was clearly slowed with low Na+ solution or Ni2+. Vanadate also slightly slowed the declining phase. The declining phase was much more clearly slowed with La3+. The response to thapsigargin, a specific endoplasmic reticulum Ca2+ ATPase inhibitor, was much more clearly prolonged by those interventions. These results strongly imply the presence of Na(2+)-Ca2+ exchange and Ca2+ ATPase in the plasma membrane, and suggest that not only Ca2+ uptake into the internal stores but also Na(+)-Ca2+ exchange and plasma membrane Ca2+ ATPase have a physiological role in reducing [Ca2+]i elevated by receptor agonists and endoplasmic reticulum Ca(2+)-ATPase inhibitors in cultured human aortic endothelial cells.