Abstract
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. Inhibition of PBL proliferation with drugs specific for different steps of G0/G1/S transit prevented both blast-transformation and an increase in K+ content per cell protein. Determination of the water content in cells by measuring the density of cells in the Percoll gradient showed that, unlike the K+ content, the concentration of K+ in cell water remains unchanged, since water and K+ change in parallel. Correlation of proliferation with high cell K+ and water content has been confirmed by the data obtained in comparative study of PBL and permanently cycling Jurkat cells. Our data suggest that K+ is important for successful proliferation as the main intracellular ion that participates in regulation of cell water content during cell transition from quiescence to proliferation. We concluded that high K+ content in cells and the associated high water content is a characteristic feature of proliferating cells.
Highlights
Many evidence shows that K+ ions are required for cell proliferation, changes in intracellular K+ concentration during transition of cells from quiescence to cycling are insufficiently studied
We show that cell water content per cell protein calculated from cell buoyant density, is higher in activated than in resting peripheral blood lymphocytes (PBL) and cellular K+ concentration does not change during lymphocyte transition to proliferation
We confirmed our previous report that in human PBL stimulated by mitogenic PHA transition from quiescence to proliferation is accompanied by long-term increase in cell K+ content[28]
Summary
Many evidence shows that K+ ions are required for cell proliferation, changes in intracellular K+ concentration during transition of cells from quiescence to cycling are insufficiently studied. We concluded that high K+ content in cells and the associated high water content is a characteristic feature of proliferating cells Intracellular monovalent ions such as K+, Na+, Cl− are important for successful proliferation[1,2,3,4,5,6,7]. We present new evidence that in human PBL, stimulated to exit from quiescence (G0) to cell cycle, K+ content per cell protein rises gradually in the course of IL-2-dependent transition of small resting T lymphocytes from G0 into large blasts and DNA synthesis. We show that cell water content per cell protein calculated from cell buoyant density, is higher in activated than in resting PBL and cellular K+ concentration does not change during lymphocyte transition to proliferation. It is concluded that high cell K+ content per cell protein content as a sign of higher cellular hydration is a hallmark of cell proliferation and transformation
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