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. 2015 Jul 22;35(29):10460–10473. doi: 10.1523/JNEUROSCI.0045-15.2015

Figure 2.

Figure 2.

Mechanisms underlying astroglial Ca2+ responses to decreases in PO2. A, Representative traces of the hypoxia-induced changes in the rate of mitochondrial ROS production in individual astrocytes in culture. Responses are blocked by the mitochondrial ROS scavenger MitoQ or after mitochondrial depolarization induced by FCCP (0.5 μm). B, Hypoxia-induced [Ca2+]i responses in cultured astrocytes are blocked by FCCP (0.5 μm), MitoQ, or vitamin E (α-tocopherol). C, Group data obtained in anesthetized rats illustrating blockade of hypoxia-induced [Ca2+]i responses in cortical astrocytes after application of FCCP (10 μm). D, [Ca2+]i responses in cultured astrocytes induced by P2 receptor activation (ATP, 10 μm) in control conditions and after treatment with FCCP (0.5 μm). E, Hypoxia fails to evoke Ca2+ responses in cultured astrocytes of PINK1 knock-out (KO) mice. WT, Wild-type. F, Cultured astrocytes display Ca2+ responses to hypoxia after removal of external Ca2+, whereas depletion of the ER Ca2+ pools by thapsigargin abolishes the responses. Arrow indicates the time of thapsigargin application. G, Hypoxia fails to evoke Ca2+ responses in cultured astrocytes in the presence of PLC inhibitor (U73122) or IP3 antagonist [Xestospongin C (Xesto C)]. H, Hypoxia increases the rate of lipid peroxidation in cultured astrocytes. Right, Pseudocolored images showing changes in BODIPY 581/591 C11 fluorescence taken before and at the peak of the response induced by hypoxia. I, Summary data illustrating the effect of mitochondrial depolarization induced by FCCP (0.5 μm) on the rate of mitochondrial ROS production (reported by MitoSOX) and lipid peroxidation (reported by BODIPY 581/591 C11) in cultured astrocytes. J, Group data of the pharmacology of Ca2+ responses induced in astrocytes by decreases in PO2, suggesting that hypoxia leads to inhibition of mitochondrial respiration, ROS production, lipid peroxidation, activation of PLC, IP3 receptors, and recruitment of Ca2+ from the intracellular stores. SDT, Sodium dithionite. ***p < 0.001.