Changes in membrane potential during the progression of MCF‐7 human mammary tumor cells through the cell cycle

Abstract

We previously reported that MCF‐7 cells were arrested in the G0/G1 phase of the cell cycle by agents known to block the activity of ATP‐sensitive potassium channels (Woodfork et al., 1995, J. Cell Physiol. 162:163–171). The goal of our current study was to determine if MCF‐7 cells undergo changes in membrane potential during the cell cycle that might be linked to changes in K permeability. The resting membrane potentials of unsynchronized MCF‐7 cells during exponential growth phase were measured using sharp glass microelectrodes, and they ranged from −58.6 mV to −2.7 mV. The distribution of membrane potentials was best fitted by the sum of four Gaussian distributions with means of −9.0 mV, −17.4 mV, −24.6 mV, and −40.4 mV. These membrane potential groups were designated D (depolarized), ID (intermediate depolarized), IH (intermediate hyperpolarized), and H (hyperpolarized), respectively. The membrane potential was sensitive to the substitution of external K and Na but not Cl. The K:Na permeability ratio increased in proportion to the negativity of the membrane potential. MCF‐7 cells pharmacologically arrested in G0/G1 phase were depolarized compared to control, with cells shifted from the H and IH groups to the D group. Tamoxifen‐arrested cells chased from G0/G1 into S phase by the addition of mitogenic concentrations of 17β‐estradiol were not depolarized, and these cells were shifted from the D group back to the IH and H groups. We conclude that MCF‐7 cells hyperpolarize during passage through G0/G1 and into S phase, and this hyperpolarization probably results from an increase in the relative permeability of the plasma membrane to K. © 1995 Wiley‐Liss Inc.