Abstract

To survive, cells are able to adapt to a wide range of adverse conditions, such as varying pH from optimal (~7.4). They do this through mechanisms including acid-sensing ion channels, which alter cytosolic ion content and thus the cell’s electrophysiological profile. However, the impact of this adaptation on cellular electrophysiology remains unexplored. We investigated the effects of culture at a range of extracellular pH on the electrophysiological features of breast cancer cell lines MDA-MB-231 and MCF-7. Cells were subject to an acid–neutral–base pH from 3.0 to 9.2, after which their membrane potential (Vm), cytoplasm conductivity σcyto, effective membrane conductance Geff, and ζ-potential were measured. Cells were also analyzed after permeabilization, to examine whether observed changes were due to cell surface chemistry, or to Vm. Both cell lines exhibited different electrophysiological phenotypes in acidic environments (pH < 6.7); MDA-MB-231 exhibited statistically significant differences in ζ-potential, Vm, Geff and σcyto; MCF-7 only exhibited significant differences in σcyto. These findings suggest cells adapt to acidic microenvironments by altering Vm and potentially ζ-potential, reducing the extracellular potential, and hence potentially lowering proton concentration at the extracellular membrane surface. This offers new insights into potential therapeutic avenues to target the pH-dependent adaptations of cancer cells.

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