The Role of Intracellular Potassium in Cell Quiescence, Proliferation, and Death.

This brief review explores the role of intracellular K during the transition of cells from quiescence to proliferation and the induction of apoptosis. We focus on the relationship between intracellular K and the growth and proliferation rates of different cells, including transformed cells in culture as well as human quiescent T cells and mesenchymal stem cells, and analyze the concomitant changes in K and water content in both proliferating and apoptotic cells. Evidence is discussed indicating that during the initiation of cell proliferation and apoptosis changes in the K content in cells occur in parallel with changes in water content and therefore do not lead to significant changes in the intracellular K concentration.

Unidirectional fluxes of monovalent ions in human erythrocytes compared with lymphoid U937 cells: Transient processes after stopping the sodium pump and in response to osmotic challenge.

Recently, we have developed software that allows, using a minimum of required experimental data, to find the characteristics of ion homeostasis and a list of all unidirectional fluxes of monovalent ions through the main pathways in the cell membrane both in a balanced state and during the transient processes. Our approach has been successfully validated in human proliferating lymphoid U937 cells during transient processes after stopping the Na/K pump by ouabain and for staurosporine-induced apoptosis. In present study, we used this approach to find the characteristics of ion homeostasis and the monovalent ion fluxes through the cell membrane of human erythrocytes in a resting state and during the transient processes after stopping the Na/K pump with ouabain and in response to osmotic challenge.

Mesenchymal Stem/Stromal Cells in Three-Dimensional Cell Culture: Ion Homeostasis and Ouabain-Induced Apoptosis.

This study describes the changes in ion homeostasis of human endometrial mesenchymal stem/stromal cells (eMSCs) during the formation of three-dimensional (3D) cell structures (spheroids) and investigates the conditions for apoptosis induction in 3D eMSCs. Detached from the monolayer culture, (2D) eMSCs accumulate Na and have dissipated transmembrane ion gradients, while in compact spheroids, eMSCs restore the lower Na content and the high K/Na ratio characteristic of functionally active cells. Organized as spheroids, eMSCs are non-proliferating cells with an active Na/K pump and a lower K content per g cell protein, which is typical for quiescent cells and a mean lower water content (lower hydration) in 3D eMSCs.

Monovalent ions and stress-induced senescence in human mesenchymal endometrial stem/stromal cells.

Monovalent ions are involved in growth, proliferation, differentiation of cells as well as in their death. This work concerns the ion homeostasis during senescence induction in human mesenchymal endometrium stem/stromal cells (hMESCs): hMESCs subjected to oxidative stress (sublethal pulse of HO) enter the premature senescence accompanied by persistent DNA damage, irreversible cell cycle arrest, increased expression of the cell cycle inhibitors (p53, p21) cell hypertrophy, enhanced β-galactosidase activity. Using flame photometry to estimate K, Na content and Rb (K) fluxes we found that during the senescence development in stress-induced hMESCs, Na/Kpump-mediated K fluxes are enhanced due to the increased Na content in senescent cells, while ouabain-resistant K fluxes remain unchanged.

Intracellular K and water content in human blood lymphocytes during transition from quiescence to proliferation.

Many evidence shows that K ions are required for cell proliferation, however, changes in intracellular K concentration during transition of cells from quiescence to cycling are insufficiently studied. Here, we show using flame emission assay that a long-term increase in cell K content per g cell protein is a mandatory factor for transition of quiescent human peripheral blood lymphocytes (PBL) to proliferation induced by phytohemagglutinin, phorbol ester with ionomycin, and anti-CD3 antibodies with interleukin-2 (IL-2). The long-term increase in K content is associated with IL-2-dependent stage of PBL activation and accompanies the growth of small lymphocytes and their transformation into blasts.