scholarly journals Cation-Chloride Cotransporters, Na/K Pump, and Channels in Cell Water and Ion Regulation: In silico and Experimental Studies of the U937 Cells Under Stopping the Pump and During Regulatory Volume Decrease

2021 ◽  
Vol 9 ◽  
Author(s):  
Valentina E. Yurinskaya ◽  
Alexey A. Vereninov
Keyword(s):  
Cell Membrane ◽  
Cellular Response ◽  
Sodium Pump ◽  
Regulatory Volume Decrease ◽  
Membrane Transporters ◽  
Lymphoid Cells ◽  
Ionic Homeostasis ◽  
Ion Regulation ◽  
Monovalent Ions ◽  
Volume Decrease

Cation-coupled chloride cotransporters play a key role in generating the Cl– electrochemical gradient on the cell membrane, which is important for regulation of many cellular processes. However, a quantitative analysis of the interplay between numerous membrane transporters and channels in maintaining cell ionic homeostasis is still undeveloped. Here, we demonstrate a recently developed approach on how to predict cell ionic homeostasis dynamics when stopping the sodium pump in human lymphoid cells U937. The results demonstrate the reliability of the approach and provide the first quantitative description of unidirectional monovalent ion fluxes through the plasma membrane of an animal cell, considering all the main types of cation-coupled chloride cotransporters operating in a system with the sodium pump and electroconductive K+, Na+, and Cl– channels. The same approach was used to study ionic and water balance changes associated with regulatory volume decrease (RVD), a well-known cellular response underlying the adaptation of animal cells to a hypoosmolar environment. A computational analysis of cell as an electrochemical system demonstrates that RVD may happen without any changes in the properties of membrane transporters and channels due to time-dependent changes in electrochemical ion gradients. The proposed approach is applicable when studying truly active regulatory processes mediated by the intracellular signaling network. The developed software can be useful for calculation of the balance of the unidirectional fluxes of monovalent ions across the cell membrane of various cells under various conditions.

scholarly journals Cation-chloride cotransporters, Na/K pump, and channels in cell water and ions regulation: in silico and experimental studies of the U937 cells under stopping the pump and during RVD

2021 ◽  
Author(s):  
Alexey A Vereninov ◽  
Valentina Yurinskaya
Keyword(s):  
Plasma Membrane ◽  
Cell Membrane ◽  
Real Time ◽  
Intracellular Signaling ◽  
Ion Homeostasis ◽  
Regulatory Volume Decrease ◽  
Experimental Studies ◽  
U937 Cells ◽  
Ionic Homeostasis ◽  
Monovalent Ions

Cation-coupled chloride cotransporters play a key role in generating the Cl− electrochemical gradient on the cell membrane which is important for regulation of many cellular processes. However, the cooperation of transporters and channels of the plasma membrane in holding the ionic homeostasis of the whole cell remains poorly characterized because of the lack of a suitable tool for its computation. Our software successfully predicted in real-time changes in the ion homeostasis of U937 cells after stopping the Na/K pump, but so far considered the model with only NC cotransporter. Here the model with all main types of cotransporters is used in computation of the rearrangements of ionic homeostasis due to stopping the pump and associated with the regulatory volume decrease (RVD) of cells swollen in hypoosmolar medium. The parameters obtained for the real U937 cells are used. Successful prediction of changes in ion homeostasis in real-time after stopping the pump using the model with all major cotransporters indicates that the model is reliable. Using this model for analysis RVD showed that there is a "physical" RVD, associated with the time-dependent changes in electrochemical ion gradients, but not with alteration of channels and transporters of the plasma membrane that should be considered in studies of truly active regulatory processes mediated by the intracellular signaling network. The developed software can be useful for calculation of the balance of the partial unidirectional fluxes of monovalent ions across the cell membrane of various cells under various conditions.

Responses of lymphocytes to anisotonic media: volume-regulating behavior

1984 ◽  
Vol 246 (3) ◽  
pp. C204-C215 ◽  
Author(s):  
S. Grinstein ◽  
A. Rothstein ◽  
B. Sarkadi ◽  
E. W. Gelfand
Keyword(s):  
Regulatory Volume Decrease ◽  
Lymphocyte Subpopulations ◽  
Lymphoid Cells ◽  
Ionophore A23187 ◽  
Volume Increase ◽  
Regulatory Volume Increase ◽  
Cytoplasmic Acidification ◽  
Tissue Of Origin ◽  
Volume Decrease ◽  
Media Volume

The regulatory responses elicited in lymphoid cells suspended in anisotonic media are reviewed. The immediate response approximates osmometric behavior. In addition, in hypotonic media, the initial osmometric swelling is followed by a regulatory volume decrease (RVD), which is associated with KCl loss. The volume-induced effluxes of K+ and Cl- are mediated by two independent conductive pathways. Ca2+-depletion experiments and studies of inhibitor susceptibility suggest that Ca2+ may mediate the activation of the K+ pathway. The responses of the two main lymphocyte subpopulations to hypotonic challenge are different. RVD is much more rapid in T- than in B-cells, regardless of their tissue of origin. Under certain conditions, shrunken lymphocytes will regain their initial volume. This regulatory volume increase (RVI) is due to NaCl uptake, followed by a secondary exchange of Na+ for K+ via the Na+-K+ pump. Na+ is primarily taken up in exchange for H+ through an amiloride-sensitive pathway, whereas Cl- enters in exchange for HCO-3 (or OH-). Anion and cation fluxes responsible for RVI are electroneutral. Some of the volume-sensitive pathways can also be activated in isotonic cells. The conductive K+ pathway is activated by Ca2+ plus ionophore A23187, and the Na+-H+ exchanger can be activated by cytoplasmic acidification. The responses of lymphocytes to anisotonic challenge are compared with those of other cells, and the possible significance of the volume-induced fluxes is discussed.

Uncoupling of K+ and Cl− transport across the cell membrane in the process of regulatory volume decrease

2012 ◽  
Vol 84 (3) ◽  
pp. 292-302 ◽  
Author(s):  
Linjie Yang ◽  
Linyan Zhu ◽  
Yue Xu ◽  
Haifeng Zhang ◽  
Wencai Ye ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Regulatory Volume Decrease ◽  
Cl Transport ◽  
Volume Decrease

Studies on Human Porin XXII: Cell Membrane Integrated Human Porin Channels Are Involved in Regulatory Volume Decrease (RVD) of HeLa Cells

2000 ◽  
Vol 69 (4) ◽  
pp. 331-337 ◽  
Author(s):  
Friedrich P. Thinnes ◽  
Klaus P. Hellmann ◽  
Thea Hellmann ◽  
Rolf Merker ◽  
Ulrike Brockhaus-Pruchniewicz ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Hela Cells ◽  
Regulatory Volume Decrease ◽  
Volume Decrease

Human Platelets Exposed to Mechanical Stresses Express a Potent Lipoxygenase Product

1992 ◽  
Vol 68 (05) ◽  
pp. 589-594 ◽  
Author(s):  
Alon Margalit ◽  
Avinoam A Livne
Keyword(s):  
Regulatory Volume Decrease ◽  
Human Platelets ◽  
Mechanical Stresses ◽  
Arterial Stenosis ◽  
Platelet Suspension ◽  
Suspension Flows ◽  
Lipoxygenase Product ◽  
Pathological Conditions ◽  
K Permeability ◽  
Volume Decrease

SummaryHuman platelets exposed to hypotonicity undergo regulatory volume decrease (RVD), controlled by a potent, yet labile, lipoxygenase product (LP). LP is synthesized and excreted during RVD affecting selectively K+ permeability. LP is assayed by its capacity to reconstitute RVD when lipoxygenase is blocked. Centrifugation for preparing washed platelets (1,550 × g, 10 min) is sufficient to express LP activity, with declining potency in repeated centrifugations, indicating that it is not readily replenish-able. When platelet suspension flows in a vinyl tubing (1 mm i.d.), at physiological velocity, controlled at 90–254 cm/s, LP formation increases as a function of velocity but declines as result of increasing the tubing length. Stirring the platelets in an aggregometer cuvette for 30 s, yields no LP unless the stirring is intermittent. No associated platelet lysis or aggregation are observed following the mechanical stress applications. These results demonstrate that although mechanical stresses result in LP production, the mode of its application plays a major role. These results may indicate that LP is synthesized under pathological conditions and could be of relevance to platelets behavior related to arterial stenosis.

3D printed permeation module to monitor interaction of cell membrane transporters with exogenic compounds in real-time

2021 ◽  
Vol 1153 ◽  
pp. 338296
Author(s):  
Hana Sklenářová ◽  
Michaela Rosecká ◽  
Burkhard Horstkotte ◽  
Petr Pávek ◽  
Manuel Miró ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Real Time ◽  
Membrane Transporters ◽  
3D Printed

LRRC8A is essential for swelling‐activated chloride current and for regulatory volume decrease in astrocytes

2018 ◽  
Vol 33 (1) ◽  
pp. 101-113 ◽  
Author(s):  
Francesco Formaggio ◽  
Emanuela Saracino ◽  
Maria Grazia Mola ◽  
Shreyas Balachandra Rao ◽  
Mahmood Amiry-Moghaddam ◽  
...  
Keyword(s):  
Regulatory Volume Decrease ◽  
Chloride Current ◽  
Volume Decrease

Estrogen-related receptor γ2 controls NaCl uptake to maintain ionic homeostasis

2021 ◽  
Author(s):  
Shang-Wu Shih ◽  
Jia-Jiun Yan ◽  
Yi-Hsing Wang ◽  
Yi-Ling Tsou ◽  
Ling Chiu ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Body Fluid ◽  
Whole Body ◽  
Ionic Homeostasis ◽  
Ion Regulation ◽  
Expression Levels ◽  
Morpholino Knockdown ◽  
Oryzias Melastigma ◽  
Euryhaline Teleost

Estrogen-related receptors (ERRs) are known to function in mammalian kidney as key regulators of ion transport-related genes; however, a comprehensive understanding of the physiological functions of ERRs in vertebrate body fluid ionic homeostasis is still elusive. Here, we used medaka (Oryzias melastigma), a euryhaline teleost, to investigate how ERRs are involved in ion regulation. After transferring medaka from hypertonic seawater to hypotonic freshwater (FW), the mRNA expression levels of errγ2 were highly upregulated, suggesting that ERRγ2 may play a crucial role in ion uptake. In situ hybridization and immunofluorescence staining showed that errγ2 was specifically expressed in ionocytes, the cells responsible for Na+/Cl- transport. In normal FW, ERRγ2 morpholino knockdown caused reductions in the mRNA expression of Na+/Cl- cotransporter (NCC), the number of NCC ionocytes, Na+/Cl- influxes of ionocytes, and whole-body Na+/Cl- contents. In FW with low Na+ and low Cl-, the expression levels of mRNA for Na+/H+ exchanger 3 (NHE3) and NCC were both decreased in ERRγ2 morphants. Treating embryos with DY131, an agonist of ERRγ, increased the whole-body Na+/Cl- contents and ncc mRNA expression in ERRγ2 morphants. As such, medaka ERRγ2 may control Na+/Cl- uptake by regulating ncc and/or nhe3 mRNA expression and ionocyte number, and these regulatory actions may be subtly adjusted depending on internal and external ion concentrations. These findings not only provide new insights into the underpinning mechanism of actions of ERRs, but also enhance our understanding of their roles in body fluid ionic homeostasis for adaptation to changing environments during vertebrate evolution.

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