Oscillations: a key event in transformed renal epithelial cells
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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.
Key wordsMDCK cell Intracellular pH Intracellular Ca2+ K+ channel Oscillation Cell transformation
calcium-induced calcium release
Madin-Darby canine kidney
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- 1.Biermann AJ, Cragoe EJ, De Laat SW, Moolenaar WH (1988) Bicarbonate determines cytoplasmic pH and suppresses mitogen-induced alkalinization. J Biol Chem 263:1523–1526.Google Scholar
- 7.Grinstein S (1988) Na+/H+ exchange. CRC Press, Florida.Google Scholar
- 20.Oberleithner H, Schuricht B, Wünsch S, Schneider S (1992) Role of H+ ions in DNA packing of epithelial cell nuclei. Pflügers Arch (submitted).Google Scholar
- 27.Schwab A, Geibel J, Wang W, Oberleithner H, Giebisch G (1992) Mechanism of activation of K+ channels by minoxidil-sulfate in Madin-Darby canine kidney cells. J Membr Biol (submitted).Google Scholar