Blebbing, free Ca2+ and mitochondrial membrane potential preceding cell death in hepatocytes

Nature. 1987 Jan 1-7;325(6099):78-81. doi: 10.1038/325078a0.


Cell surface 'blebbing' is an early consequence of hypoxic and toxic injury to cells. A rise in cytosolic free Ca2+ has been suggested as the stimulus for bleb formation and the final common pathway to irreversible cell injury. Here, using digitized low-light video microscopy, we examine blebbing, cytosolic free Ca2+, mitochondrial membrane potential and loss of cell viability in individual cultured hepatocytes. Unexpectedly, we found that after 'chemical hypoxia' with cyanide and iodoacetate, cytosolic free Ca2+ does not change during bleb formation or before loss of cellular viability. Cell death was precipitated by a sudden breakdown of the plasma membrane permeability barrier, possibly caused by rupture of a cell surface bleb.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Triphosphate / biosynthesis
  • Animals
  • Calcium / metabolism*
  • Cell Survival
  • Egtazic Acid / pharmacology
  • Epidermal Growth Factor / pharmacology
  • Ethers / pharmacology
  • Hypoxia / pathology
  • Ionomycin
  • Liver / cytology*
  • Membrane Potentials
  • Mitochondria, Liver / physiology*
  • Phenylephrine / pharmacology
  • Rats
  • Time Factors
  • Vasopressins / pharmacology


  • Ethers
  • Vasopressins
  • Phenylephrine
  • Egtazic Acid
  • Ionomycin
  • Epidermal Growth Factor
  • Adenosine Triphosphate
  • Calcium