CHANGES IN MEMBRANE-POTENTIAL DURING THE PROGRESSION OF MCF-7 HUMAN MAMMARY-TUMOR CELLS THROUGH THE CELL-CYCLE

We previously reported that MCF-7 cells were arrested in the G0/G1 pha se of the cell cycle by agents known to block the activity of ATP-sens itive potassium channels (Woodfork et al., 1995, J. Cell Physiol. 162: 163-171). The goal of our current study was to determine ii MCF-7 cell s undergo changes in membrane potential during the cell cycle that mig ht be linked to changes in K permeability. The resting membrane potent ials of unsynchronized MCF-7 cells during exponential growth phase wer e measured using sharp glass microelectrodes, and they ranged from -58 .6 mV to -2.7 mV. The distribution of membrane potentials was best fit ted by the sum of four Gaussian distributions with means oi -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 (interme diate hyperpolarized), and H (hyperpolarized), respectively. The membr ane potential was sensitive to the substitution of external K and Na b ut not CI. The K:Na permeability ratio increased in proportion to the negativity of the membrane potential. MCF-7 cells pharmacologically ar rested in G0/G1 phase were depolarized compared to control, with cells shifted from the H and IH groups to the D group. Tamoxifen-arrested c ells chased from G0/G1 into S phase by the addition of mitogenic conce ntrations of 17 beta-estradiol were not depolarized, and these cells w ere 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 i n the relative permeability of the plasma membrane to K. (C) 1995 Wile y-Liss, Inc.