The Journal of Membrane Biology

, Volume 205, Issue 3, pp 147–157 | Cite as

Ion Channels in Cell Proliferation and Apoptotic Cell Death

  • F. Lang
  • M. Föller
  • K.S. Lang
  • P.A. Lang
  • M. Ritter
  • E. Gulbins
  • A. Vereninov
  • S.M. Huber


Cell proliferation and apoptosis are paralleled by altered regulation of ion channels that play an active part in the signaling of those fundamental cellular mechanisms. Cell proliferation must - at some time point - increase cell volume and apoptosis is typically paralleled by cell shrinkage. Cell volume changes require the participation of ion transport across the cell membrane, including appropriate activity of Cl and K+ channels. Besides regulating cytosolic Cl activity, osmolyte flux and, thus, cell volume, most Cl channels allow HCO3 exit and cytosolic acidification, which inhibits cell proliferation and favors apoptosis. K+ exit through K+ channels may decrease intracellular K+ concentration, which in turn favors apoptotic cell death. K+ channel activity further maintains the cell membrane potential, a critical determinant of Ca2+ entry through Ca2+ channels. Cytosolic Ca2+ may trigger mechanisms required for cell proliferation and stimulate enzymes executing apoptosis. The switch between cell proliferation and apoptosis apparently depends on the magnitude and temporal organization of Ca2+ entry and on the functional state of the cell. Due to complex interaction with other signaling pathways, a given ion channel may play a dual role in both cell proliferation and apoptosis. Thus, specific ion channel blockers may abrogate both fundamental cellular mechanisms, depending on cell type, regulatory environment and condition of the cell. Clearly, considerable further experimental effort is required to fully understand the complex interplay between ion channels, cell proliferation and apoptosis.


CD95/Fas Scramblase PGE2 Cell volume Lymphocytes Erythrocytes 



The authors acknowledge the meticulous preparation of the manuscript by Lejla Subasic. The work of the authors was supported by the Deutsche Forschungsgemeinschaft, Nr. La 315/4-3, La 315/6-1, Le 792/3-3, DFG Schwerpunkt Intrazelluläre Lebensformen La 315/11-1, and Bundesministerium für Bildung, Wissenschaft, Forschung und Technologic (Center for Interdisciplinary Clinical Research) 01 KS 9602.


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Copyright information

© Springer Science+Business Media, Inc. 2005

Authors and Affiliations

  • F. Lang
    • 1
  • M. Föller
    • 1
  • K.S. Lang
    • 1
  • P.A. Lang
    • 1
  • M. Ritter
    • 2
  • E. Gulbins
    • 1
  • A. Vereninov
    • 3
  • S.M. Huber
    • 1
  1. 1.Department of PhysiologyUniversity of TübingenGermany
  2. 2.Department of PhysiologyUniversity of SalzburgAustria
  3. 3.Institute of CytologyRussian Academy of SciencesSt. PetersburgRussia

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