The Journal of Membrane Biology

, Volume 209, Issue 1, pp 43–58 | Cite as

Potential Roles of Electrogenic Ion Transport and Plasma Membrane Depolarization in Apoptosis

  • R. Franco
  • C.D. Bortner
  • J.A. CidlowskiEmail author


Apoptosis is characterized by the programmed activation of specific biochemical pathways leading to the organized demise of cells. To date, aspects of the intracellular signaling machinery involved in this phenomenon have been extensively dissected and characterized. However, recent studies have elucidated a novel role for changes in the intracellular milieu of the cells as important modulators of the cell death program. Specially, intracellular ionic homeostasis has been reported to be a determinant in both the activation and progression of the apoptotic cascade. Several apoptotic insults trigger specific changes in ionic gradients across the plasma membrane leading to depolarization of the plasma membrane potential (PMP). These changes lead to ionic imbalance early during apoptosis. Several studies have also suggested the activation and/or modulation of specific ionic transport mechanisms including ion channels, transporters and ATPases, as mediators of altered intracellular ionic homeostasis leading to PMP depolarization during apoptosis. However, the role of PMP depolarization and of the changes in ionic homeostasis during the progression of apoptosis are still unclear. This review summarizes the current knowledge regarding the causes and consequences of PMP depolarization during apoptosis. We also review the potential electrogenic ion transport mechanisms associated with this event, including the net influx/efflux of cations and anions. An understanding of these mechamisms could lead to the generation of new therapeutic approaches for a variety of diseases involving apoptosis.


Apoptotic volume decrease ATPases Cell death Cell signaling Cell volume Electrogenic transport Ion channels Ion flux Ion transporters Ionic gradients Ionic homeostasis Plasma membrane potential 



apoptotic volume decrease;


plasma membrane potential;


regulatory volume decrease;


voltage-gated Na+ channel;


voltage-gated Ca2+ channels.



We appreciate the input of Dr. James W. Jr. Putney.


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© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  1. 1.Laboratory of Signal TransductionNational Institute of Environmental Health Sciences, National Institutes of HealthUSA

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