Ultrastruct pathology of phalloidin-intoxicated hepatocytes in the presence and absence of extracellular calcium.
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.
D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002478:Cells, Cultured; D003571:Cytochalasin B / Q000494:pharmacology; D003599:Cytoskeleton / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology; D005260:Female; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000648:ultrastructure*; D008854:Microscopy, Electron; D008933:Mitochondrial Swelling / Q000187:drug effects; D009842:Oligopeptides / Q000633:toxicity*; D010590:Phalloidine / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains
D009842:Oligopeptides; D010590:Phalloidine; D003571:Cytochalasin B; D000431:Ethanol; D002118:Calcium