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Herz

, Volume 24, Issue 3, pp 232–235 | Cite as

Cell volume regulatory mechanisms in apoptotic cell death

  • Florian Lang
  • Anne C. Uhlemann
  • Albrecht Lepple-Wienhues
  • Ildiko Szabo
  • Detlef Siemen
  • Bernd Nilius
  • Erich Gulbins
Article

Abstract

One of the hallmarks of apoptosis is cell shrinkage, which — at constant extracellular osmolarity — requires a decrease of cellular osmolarity. Moreover, apoptosis can be elicited by increase of extracellular osmolarity and the resistance of cells towards apoptosis correlates with their ability to regulate their volume in hypertonic environment. On the other hand, CD95-receptor-mediated apoptosis is blunted at moderate increases of extracellular osmolarity. Given the role of cell volume alterations it is not surprising that apoptosis is paralleled by marked alterations of cell volume regulatory mechanisms. Stimulation of the CD95-receptor, which confers apoptosis to a variety of cells, leads to activation of cell volume regulatory anion channel ORCC. However, activation of ORCC is paralleled by inhibition of cell volume regulatory K+ channel Kv1.3. It is only 40 to 60 minutes after triggering of the CD95-receptor when the cells release the organic osmolyte taurine and shrink.

Key Words

Cell volume K+ channels Cl channels Osmolytes Apoptosis Lymphocytes 

Zellvolumenregulierende Mechanismen bei apoptotischem Zelltod

Zusammenfassung

Eines der charakteristischen Kennzeichen von Apoptose ist Zellschrumpfung, die eine Abnahme der zellulären Osmolarität erfordert. Dies ist ohne Beteiligung zellvolumenregulierender Mechanismen nicht möglich. Bei der Zellvolumenregulation können die Zellen durch Elektrolytaufnahme über Na+/H+-Austauscher, Na+, K+, 2Cl-Kotransport und Na+-Kanäle schwellen sowie durch Elektrolytverlust über Ionenkanäle (K+-Kanäle und Cl-Kanäle) und KCl-Symport schrumpfen. Darüber hinaus können Zellen durch Aufnahme oder Bildung von organischen Osmolyten (unter anderem Sorbitol, Inositol, Betain, Glycerophosphorylcholin und Taurin) ihre Osmolarität und damit ihr Volumen steigern und durch Osmolytabgabe ihre Osmolarität senken. Apoptose kann durch massive osmotische Zellschrumpfung ausgelöst werden, und die Fähigkeit von Zellen, einen hyperosmolaren Schock ohne Apoptose zu überstehen, korreliert mit ihrer Fähigkeit zur Zellvolumenregulation. Die CD95-Rezeptorvermittelte Apoptose von Jurkat-T-Lymphozyten wird andererseits durch moderate osmotische Zellschrumpfung gehemmt. Angesichts der Bedeutung des Zellvolumens für die Apoptose überrascht es nicht, daß die rezeptorvermittelte Apoptose von veränderter Aktivität zellvolumenregulierter Transportprozesse an der Zellmembran begleitet ist. Stimulation des CD95-Rezeptors führt zur Aktivierung der zellvolumenregulierten Anionenkanäle OrCC (outwardly rectifying chloride channels), jedoch gleichzeitig zur Hemmung der zellvolumenregulierten K+-Kanäle Kv1.3. Erst etwa 60 Minuten nach Aktivierung des CD95-Rezeptors kommt es zur Zellschrumpfung. Dabei eliminieren die Zellen den organischen Osmolyten Taurin.

Schlüsselwörter

Zellvolumen K+-Kanäle Cl-Kanäle Osmolyte Apoptose Lymphozyten 

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Copyright information

© Urban & Vogel 1999

Authors and Affiliations

  • Florian Lang
    • 1
  • Anne C. Uhlemann
    • 1
  • Albrecht Lepple-Wienhues
    • 1
  • Ildiko Szabo
    • 1
  • Detlef Siemen
    • 1
  • Bernd Nilius
    • 2
  • Erich Gulbins
    • 1
  1. 1.Department for PhysiologyUniversity of TübingenTübingenGermany
  2. 2.University of LeuvenLeuven

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