Unidirectional Flux Balance of Monovalent Ions in Cells with Na/Na and Li/Na Exchange: Experimental and Computational Studies on Lymphoid U937 Cellsстатья
Статья опубликована в высокорейтинговом журнале
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Дата последнего поиска статьи во внешних источниках: 4 апреля 2017 г.
Аннотация:Monovalent ion traffic across the cell membrane occurs via various pathways. Evaluation of
individual fluxes in whole cell is hampered by their strong interdependence. This difficulty
can be overcome by computational analysis of the whole cell flux balance. However, the
previous computational studies disregarded ion movement of the self-exchange type. We
have taken this exchange into account. The developed software allows determination of
unidirectional fluxes of all monovalent ions via the major pathways both under the balanced
state and during transient processes. We show how the problem of finding the rate coefficients
can be solved by measurement of monovalent ion concentrations and some of the
fluxes. Interdependence of fluxes due to the mandatory conditions of electroneutrality and
osmotic balance and due to specific effects can be discriminated, enabling one to identify
specific changes in ion transfer machinery under varied conditions. To test the effectiveness
of the developed approach we made use of the fact that Li/Na exchange is known to be an
analogue of the coupled Na/Na exchange. Thus, we compared the predicted and experimental
data obtained on U937 cells under varied Li+ concentrations and following inhibition
of the sodium pump with ouabain.We found that the coupled Na/Na exchange in U937 cells
comprises a significant portion of the entire Na+ turnover. The data showed that the loading
of the sodium pump by Li/Na exchange involved in the secondary active Li+ transport at
1–10 mM external Li+ is small. This result may be extrapolated to similar Li+ and Na+ flux
relationships in erythrocytes and other cells in patients treated with Li+ in therapeutic doses.
The developed computational approach is applicable for studying various cells and can be
useful in education for demonstrating the effects of individual transporters and channels on
ion gradients, cell water content and membrane potential.