Russo M A, Kane A B, Farber J L
Am J Pathol. 1982 Nov;109(2):133-44.
The killing of cultured hepatocytes by phalloidin can be dissociated into two phases by manipulation of the Ca2+ concentration of the medium. In the absence of extracellular Ca2+, hepatocytes are injured but not killed by phalloidin. Addition of 1.8 mM Ca2+ to the culture medium kills 60-70% of the cells by three hours. As an initial attempt to identify the mechanisms whereby Ca2+ ions irreversibly injure phalloidin-damaged hepatocytes, we have examined the ultrastructural pathology of phalloidin-intoxicated liver cells in the presence or absence of extracellular Ca2+. In the absence of extracellular Ca2+ ions, the morphologic manifestations of phalloidin intoxication reflect entirely the interaction between phalloidin, microfilaments, and the plasma membrane. In the presence of Ca2+ ions, the morphologic manifestations of the lethal effects of Ca2+ are described: the swelling of mitochondria accompanied by the accumulation of dense, amorphous precipitates; a supercontracture of microfilaments, and a loss of volume control with intracellular edema and a change in cell shape. These alterations can be attributed to the known biologic actions of Ca2+ ions on cellular structure and function. The present study allows, therefore, a preliminary identification of mechanisms by which extracellular Ca2+ ions may mediate cell death in this as well as in other similar situations.
通过控制培养基中的钙离子浓度，鬼笔环肽对培养肝细胞的杀伤作用可分为两个阶段。在无细胞外钙离子的情况下，肝细胞虽会受到鬼笔环肽的损伤，但不会被杀死。向培养基中添加1.8 mM钙离子，三小时内可杀死60% - 70%的细胞。作为初步尝试，为确定钙离子不可逆损伤鬼笔环肽损伤肝细胞的机制，我们研究了有无细胞外钙离子时鬼笔环肽中毒肝细胞的超微结构病理学。在无细胞外钙离子的情况下，鬼笔环肽中毒的形态学表现完全反映了鬼笔环肽、微丝和质膜之间的相互作用。在有钙离子的情况下，描述了钙离子致死效应的形态学表现：线粒体肿胀并伴有致密无定形沉淀物的积累；微丝超收缩，失去体积控制，细胞内出现水肿且细胞形状改变。这些改变可归因于钙离子对细胞结构和功能的已知生物学作用。因此，本研究初步确定了细胞外钙离子在这种以及其他类似情况下介导细胞死亡的机制。
