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Oscillations: a key event in transformed renal epithelial cells

  • Guest Lecture, “Gessellschaft für Nephrologie”, 23rd Congress
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Summary

Intracellular pH (pHi) plays a critical role in the entry of cells into the DNA-synthesis phase of the cell cycle. Alterations in pHi may contribute to abnormal proliferative responses such as those seen in tumorigenic cells. We observed that alkaline stress leads to genomic transformation of Madin-Darby canine kidney (MDCK) cells. Transformed cells (F cells) form “foci” in culture, lack contact inhibition, and are able to migrate, typical characteristics of dedifferentiated tumorigenic cells. F cells exhibit spontaneous biorhythmicity. Rhythmic transmembrane Ca2+ flux activates plasma membrane K+ channels and Na+/H+ exchange. This leads to periodic changes of membrane voltage and pHi at about one cycle per minute. We conclude that endogenous oscillatory activity could be a trigger mechanism for DNA synthesis, proliferation, and abnormal growth of renal epithelial cells in culture.

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Abbreviations

CICR:

calcium-induced calcium release

IP3a:

inositol triphosphate

MDCK:

Madin-Darby canine kidney

pHia:

intracellular pH

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Authors and Affiliations

  1. Physiologisches Institut der Universität Würzburg, Röntgenring 9, W-8700, Würzburg, Germany

    H. Oberleithner, A. Schwab, H. -J. Westphale & L. Wojnowski

Authors
  1. H. Oberleithner
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  2. A. Schwab
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  3. H. -J. Westphale
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  4. L. Wojnowski
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Dedicated to our friend and teacher Prof. Dr. Gerhard Giebisch in gratitude for his long standing support

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Oberleithner, H., Schwab, A., Westphale, H.J. et al. Oscillations: a key event in transformed renal epithelial cells. Clin Investig 70, 816–824 (1992). https://doi.org/10.1007/BF00180753

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