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 17 beta-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.

Blockage of intermediate-conductance-Ca2+-activated K+ channels inhibits progression of human endometrial cancer

“…Inhibition of K þ channels leads to membrane depolarization and cellcycle arrest in early G 1 phase in the MCF-7 human breast carcinoma cell line (Wang et al, 1998). Conversely, activation of K þ channels promotes the cellcycle progression from the G 0 /G 1 to S phase (Wonderlin et al, 1995;Ouadid-Ahidouch et al, 2001;Chittajallu et al, 2002). Here, we demonstrated that the activity of IKCa1 channels contributed to the progression of EC cells through the G 1 phase in the G 1 /S transition.…”

Nanoelectrochemistry of mammalian cells

“…30). To determine whether this difference results from membrane polarization that may be induced by current flowing between the intracellular nanoprobe and the external reference electrode, we measured the dependence of ⌬E 1/2 on concentration (c FcCH 2 OH ).…”

Targeting potassium channels in cancer

“…Although the membrane potential of cancer cells tends to be more depolarized, cell cycle phase-specific changes in membrane potential have been reported. MCF-7 human mammary cells display a transient hyperpolarization at G1-S transition, which was suggested to be a result of an increase in membrane permeability to potassium (Wonderlin et al, 1995;Fig. 2).…”