TY - JOUR
T1 - Ultrastructural pathology of phalloidin-intoxicated hepatocytes in the presence and absence of extracellular calcium
AU - Russo, M. A.
AU - Kane, A. B.
AU - Farber, J. L.
PY - 1982
Y1 - 1982
N2 - The killing of cultured hepatocytes by phalloidin can be dissociated into two phases by manipulation of the Ca
2+ concentration of the medium. In the absence of extracellular Ca
2+, hepatocytes are injured but not killed by phalloidin. Addition of 1.8 mM Ca
2+ to the culture medium kills 60-70% of the cells by three hours. As an initial attempt to identify the mechanisms whereby Ca
2+ ions irreversibly injure phalloidin-damaged hepatocytes, the authors have examined the ultrastructural pathology of phalloidin-intoxicated liver cells in the presence or absence of extracellular Ca
2+. In the absence of extracellular Ca
2+ ions, the morphologic manifestations of phalloidin intoxication reflect entirely the interaction between phalloidin, microfilaments, and the plasma membrane. In the presence of Ca
2+ ions, three morphologic manifestations of the lethal effects of Ca
2+ 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 Ca
2+ ions on cellular structure and function. The present study allows, therefore, a preliminary identification of mechanisms by which extracellular Ca
2+ ions may mediate cell death in this as well as in other similar situations.
AB - The killing of cultured hepatocytes by phalloidin can be dissociated into two phases by manipulation of the Ca
2+ concentration of the medium. In the absence of extracellular Ca
2+, hepatocytes are injured but not killed by phalloidin. Addition of 1.8 mM Ca
2+ to the culture medium kills 60-70% of the cells by three hours. As an initial attempt to identify the mechanisms whereby Ca
2+ ions irreversibly injure phalloidin-damaged hepatocytes, the authors have examined the ultrastructural pathology of phalloidin-intoxicated liver cells in the presence or absence of extracellular Ca
2+. In the absence of extracellular Ca
2+ ions, the morphologic manifestations of phalloidin intoxication reflect entirely the interaction between phalloidin, microfilaments, and the plasma membrane. In the presence of Ca
2+ ions, three morphologic manifestations of the lethal effects of Ca
2+ 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 Ca
2+ ions on cellular structure and function. The present study allows, therefore, a preliminary identification of mechanisms by which extracellular Ca
2+ ions may mediate cell death in this as well as in other similar situations.
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M3 - Article
C2 - 6890315
AN - SCOPUS:0020336363
VL - 109
SP - 133
EP - 144
JO - American Journal of Pathology
JF - American Journal of Pathology
SN - 0002-9440
IS - 2
ER -