Alkaline stress leads to genomic transformation of Madin-Darby canine kidney (MDCK) cells. Transformed cells are spindle shaped and pleomorphic, lacking contact inhibition and exhibiting poor adhesion to the culture support, typical characteristics of dedifferentiated tumor cells. They generate spontaneous membrane potential oscillations at a frequency of about 1/min. These oscillations are calcium-dependent and due to the periodic activation/inactivation of plasma membrane K+ channels. Cells exhibit intracellular pH transients in phase with the membrane potential oscillations due to transmembrane HCO–3 shifts. Each voltage spike is followed by a transient period of intracellular alkalosis inactivating spiking activity. Aldosterone blunts oscillations through stimulation of plasma membrane Na+/H+ exchange and subsequent intracellular alkalinization. The pH changes may play an important role in the initiation and maintenance of abnormal epithelial cell growth.
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Hans Oberleithner (1992) studied this question.