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Schafer, M., D. Bahde, B. Bosche, Y. Ladilov, C. Schafer, H. M. Piper, and T. Noll. Modulation of early [[Ca.sup.2+]].sub.i] rise in metabolically inhibited endothelial cells by xestospongin C. Am J Physiol Heart Circ Physiol 280: H1002-H1010, 2001.--When energy metabolism is disrupted, endothelial cells lose [Ca.sup.2+] from endoplasmic reticulum (ER) and the cytosolic [Ca.sup.2+] concentration ([[Ca.sup.2+]].sub.i]) increases. The importance of glycolytic energy production and the mechanism of [Ca.sup.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.sup.2+]].sub.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.sup.2+]].sub.i], while this maneuver preserved cellular ATP contents. The inhibitor of ER-[Ca.sup.2+]-ATPase, thapsigargin (10 nM), augmented the 2-DG-induced rise of [[Ca.sup.2+]].sub.i]. Xestospongin C (3 [micro]M), an inhibitor of D-myo-inositol 3-phosphate [Ins(3)P]-sensitive ER-[Ca.sup.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.sup.2+] store is discharged by opening of the Ins(3)P-sensitive release channel. Xestospongin C can effectively suppress the early [[Ca.sup.2+]].sub.i] rise in metabolically inhibited endothelial cells. D-myo-inositol 3-phosphate-sensitive [Ca.sup.2+] release; ischemia; hypoxia; cytosolic [Ca.sup.2+] concentration

Analyzes the importance of adenosine triphosphate production through glycolysis and the mechanism of calcium loss from the endoplasmic reticulum (ER). Indication that the ER of endothelial cells is very sensitive to glycolytic metabolic inhibition; Discharging of the ER calcium store by opening of the D-myo-inositol 3-phosphate-sensitive release channel.