title: 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.
authors.affiliation: Department of Pharmacology and Toxicology, Robert C. Byrd Health Sciences Center, West Virginia University, Morgantown 26506, USA.
authors.forename: W F
authors.initials: WF
authors.lastname: Wonderlin
authors.forename: K A
authors.initials: KA
authors.lastname: Woodfork
authors.forename: J S
authors.initials: JS
authors.lastname: Strobl
mesh_terms: D001943:Breast Neoplasms / Q000473:pathology* / Q000503:physiopathology; D002453:Cell Cycle / Q000187:drug effects; D004965:Estrogen Antagonists / Q000494:pharmacology; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D008564:Membrane Potentials; D026902:Potassium Channel Blockers; D011802:Quinidine / Q000494:pharmacology; D013629:Tamoxifen / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D004965:Estrogen Antagonists; D006131:Growth Inhibitors; D026902:Potassium Channel Blockers; D013629:Tamoxifen; D011802:Quinidine