When energy metabolism is disrupted, endothelial cells lose Ca2+from endoplasmic reticulum (ER) and the cytosolic Ca2+concentration ([Ca2+]i) increases. The importance of glycolytic energy production and the mechanism of Ca2+loss from the ER were analyzed. Endothelial cells from porcine aorta in culture and in situ were used as models. 2-Deoxy-d-glucose (2-DG, 10 mM), an inhibitor of glycolysis, caused an increase in [Ca2+]i(measured with fura 2) within 1 min when total cellular ATP contents were not yet affected. Stimulation of oxidative energy production with pyruvate (5 mM) did not attenuate this 2-DG-induced rise of [Ca2+]i, while this maneuver preserved cellular ATP contents. The inhibitor of ER-Ca2+-ATPase, thapsigargin (10 nM), augmented the 2-DG-induced rise of [Ca2+]i. Xestospongin C (3 μM), an inhibitor of d- myo-inositol 3-phosphate [Ins(3) P]-sensitive ER-Ca2+release, abolished the rise. The results demonstrate that the ER of endothelial cells is very sensitive to glycolytic metabolic inhibition. When this occurs, the ER Ca2+store is discharged by opening of the Ins(3) P-sensitive release channel. Xestospongin C can effectively suppress the early [Ca2+]irise in metabolically inhibited endothelial cells.
Omega-3 fatty acids and brain energy metabolism: Impact on the expression of glucose transporters and glucose transport activity in endothelial cells in culture