Membrane Potential Bistability in Human Breast Cancer MDA-MB-231 Cells: A “Hodgkin–Huxley Type” Model

The plasma membrane voltage ( V m ) is well known to have significant involvement in a wide range of cellular functions including cancer progression. Voltage imaging revealed that V m of MDA-MB-231 breast cancer cells is “bistable” with hyperpolarizing voltage transients (HVTs). Here, we formulate a model of V m incorporating the ion channels N a v 1.5 , C a v 3.2 , and K Ca 1.1 . V m is governed by the Hodgkin–Huxley formalism coupled to intracellular C a 2 + dynamics, via C a 2 + influx through C a v 3.2 and C a 2 + -dependent efflux of K + through K Ca 1.1 . Stochastic fluctuations—arising from sparse ion channel expression and C a 2 + -induced C a 2 + release (CICR)—drive V m transitions between the otherwise stable depolarized and hyperpolarized states. The model qualitatively reproduces the key experimental observations of HVTs, and their suppression by specific inhibitors of N a v 1.5 or K Ca 1.1 . It is predicted that inhibition of CICR should also lead to suppression of HVTs. Our model promises to help the understanding of the dynamic electrical activity of the MDA-MB-231 cell model and its functional consequences, and may inspire future bioelectricity-based cancer diagnosis and therapy.