| 11179041 |
Schafer M, Bahde D, Bosche B, Ladilov Y, Schafer C, Piper HM, Noll T: Modulation of early [Ca2+] i rise in metabolically inhibited endothelial cells by xestospongin C. Am J Physiol Heart Circ Physiol. 2001 Mar;280(3):H1002-10.
When energy metabolism is disrupted, endothelial cells lose Ca (2+) from endoplasmic reticulum (ER) and the cytosolic Ca (2+) concentration ([Ca (2+)](i)) increases. The importance of glycolytic energy production and the mechanism of Ca (2+) 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 [Ca (2+)](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 [Ca (2+)](i), while this maneuver preserved cellular ATP contents. The inhibitor of ER-Ca (2+)-ATPase, thapsigargin (10 nM), augmented the 2-DG-induced rise of [Ca (2+)](i). Xestospongin C (3 microM), an inhibitor of D-myo-inositol 3-phosphate [Ins (3) P]-sensitive ER-Ca (2+) 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 Ca (2+) store is discharged by opening of the Ins (3) P-sensitive release channel. Xestospongin C can effectively suppress the early [Ca (2+)](i) rise in metabolically inhibited endothelial cells. |
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