Ultrastructural pathology of phalloidin-intoxicated hepatocytes in the presence and absence of extracellular calcium

M. A. Russo, A. B. Kane, J. L. Farber

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)133-144
Number of pages12
JournalAmerican Journal of Pathology
Volume109
Issue number2
Publication statusPublished - 1982

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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