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Dynamics of the net and unidirectional K + , Na + , and Cl -fluxes in U937 cells during transition Iso-Hyper (+100 NaCl) calculated for the modelwith all main cotransporters and parameters like in cells U937 equilibrated with standard 310 mOsm medium.
Source publication
The work provides a modern mathematical description of animal cell electrochemical system under a balanced state and during the transition caused by an increase in external osmolarity, considering all the main ionic pathways in the cell membrane: the sodium pump, K+, Na+, Cl- electroconductive channels and cotransporters NC, KC, and NKCC. The descr...
Contexts in source publication
Context 1
... looks like "activation" of NKCC transporter although the intrinsic properties of cotransporter, i.e., rate coefficient in the model is not changed. The increase in the net fluxes of K + , Na + and Cl -via NKCC caused by an increase in the NKCC gradient is clearly seen if the dynamic of the unidirectional and net fluxes is considered which is shown in Table 4. The considered examples show that specific NKCC blockers like bumetanide and its analogues can have no effect on the entire ion homeostasis in normal cells. ...Context 2
... Cl -channels and KC cotransporter in cells like U937 are the main antagonists of NC cotransporterbecause this is a significant pathway for the net Cl -flux down electrochemical gradient ( Table 4, yellow lines "Before"). The pair NC cotransporter-Cl -channels is a powerful regulator of the cell water balance. ...Context 3
... is because there are other pathways for downhill movement of Cl -besides channels in the cells like U937. The channel part of the Cl -downhill net flux is only about half; the other half is the flux through the KC pathway and about 0.6 % is the flux through the NKCC cotransporter (Table 4, yellow lines "Before"). ...Citations
... Our thanks to Igor Raikov, a student of the Alferov Federal State Academic University RAS, Russia, for checking the use of the BEZ02BC file on a 32-bit computer. This manuscript has been released as a Pre-Print at BioRxiv, online Nov. 15, 2021 (Yurinskaya and Vereninov, 2021b). ...
Studying the transport of monovalent ions across the cell membrane in living cells is complicated by the strong interdependence of fluxes through parallel pathways and requires therefore computational analysis of the entire electrochemical system of the cell. Current paper shows how to calculate changes in the cell water balance and ion fluxes caused by changes in the membrane channels and transporters during a normal regulatory increase in cell volume in response to osmotic cell shrinkage (RVI) followed by a decrease in cell volume associated with apoptosis (AVD). Our recently developed software is used as a computational analysis tool and the established human lymphoid cells U937 are taken as an example of proliferating animal cells. It is found that, in contrast to countless statements in the literature that cell volume restoration requires the activation of certain ion channels and transporters, the cellular responses such as RVI and AVD can occur in an electrochemical system like U937 cells without any changes in the state of membrane channels or transporters. These responses depend on the types of chloride cotransporters in the membrane and differ in a hyperosmolar medium with additional sucrose and in a medium with additional NaCl. This finding is essential for the identification of the true changes in membrane channels and transporters responsible for RVI and AVD in living cells. It is determined which changes in membrane parameters predicted by computational analysis are consistent with experimental data obtained on living human lymphoid cells U937, Jurkat, and K562 and which are not. An essential part of the results is the developed software that allows researchers without programming experience to calculate the fluxes of monovalent ions via the main transmembrane pathways and electrochemical gradients that move ions across the membrane. The software is available for download. It is useful for studying the functional expression of the channels and transporters in living cells and understanding how the cell electrochemical system works.
