Volume Regulation in Epithelia

Larsen, Erik Hviid; Hoffmann, Else K.

doi:10.1007/978-3-030-52780-8_11

Cited by 7 publications

(6 citation statements)

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“…It is believed that specific changes in channels and transporters of the cell membrane are responsible for the regulation of cell volume under anisosmolar conditions, which are triggered by osmotic stress and can differ depending on the cell type ( Sarkadi and Parker, 1991 ; Hoffmann et al, 2009 ; Koivusalo et al, 2009 ; Hoffmann and Pedersen, 2011 ; Lang and Hoffmann, 2012 ; Jentsch, 2016 ; Pasantes-Morales, 2016 ; Delpire and Gagnon, 2018 ; Larsen and Hoffmann, 2020 ). This concept is based mostly on the studies of the effects of inhibitors and genetic cell modifications.…”

Section: Resultsmentioning

confidence: 99%

Cation-Chloride Cotransporters, Na/K Pump, and Channels in Cell Water/Ionic Balance Regulation Under Hyperosmolar Conditions: In Silico and Experimental Studies of Opposite RVI and AVD Responses of U937 Cells to Hyperosmolar Media

Yurinskaya

2022

Front. Cell Dev. Biol.

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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.

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Section: Resultsmentioning

confidence: 99%

Cation-Chloride Cotransporters, Na/K Pump, and Channels in Cell Water/Ionic Balance Regulation Under Hyperosmolar Conditions: In Silico and Experimental Studies of Opposite RVI and AVD Responses of U937 Cells to Hyperosmolar Media

Yurinskaya

2022

Front. Cell Dev. Biol.

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“…It is believed that specific changes in channels and transporters of the cell membrane are responsible for the regulation of cell volume under anisosmolar conditions, which are triggered by osmotic stress and can differ depending on the cell type [4,5,[19][20][21][22][23][24][25]. This concept is based mostly on the studies of the effects of inhibitors and genetic cell modifications.…”

Section: Rearrangement Of Ionic Homeostasis In Hyperosmolar Media At ...mentioning

confidence: 99%

Balance of Na+, K+, and Cl- Fluxes in an Animal Cell with Cation-Chloride Cotransporters, Na/K Pump and Channels Under Normal and Hyperosmolar Conditions: In Silico and Experimental Studies of RVI and AVD Responses of U937 cells

Yurinskaya,

Vereninov

2022

Prime Archives in Biosciences

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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 electrochemical system like U937 cell 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.

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“…The extension of PI(3,4,5)P3 patches, which can reach a diameter of several micrometers, reflects the balanced activity of PI3Ks and the lipid phosphatase, phosphatase and tensin homolog (PTEN), which dephosphorylates PI(3,4,5)P3 back to PI(4,5)P2. The kinetics of PI(4,5)P2 and PI(3,4,5)P3 are mechanistically linked to actin-remodeling during macropinocytosis ( Araki et al, 1996 , 2007 ; Worby and Dixon, 2014 ; Swanson and Yoshida, 2019 ; Nussinov et al, 2020 ) and to the regulation of many ion channels and transporters relevant to pinocytosis as well as CVR ( Araki et al, 1996 ; Lang et al, 1998 ; Ritter et al, 2001 ; Furst et al, 2002 ; Jakab et al, 2002 ; Okada, 2004 ; Lang, 2007 ; Suh and Hille, 2008 ; Hoffmann et al, 2009 ; Abu Jawdeh et al, 2011 ; Lang and Hoffmann, 2012 ; Balla, 2013 ; Hansen, 2015 ; Hille et al, 2015 ; Kunzelmann, 2015 ; Jentsch, 2016 ; Pasantes-Morales, 2016 ; De Los Heros et al, 2018 ; Delpire and Gagnon, 2018 ; Konig et al, 2019 ; Okada et al, 2019 ; Centeio et al, 2020 ; Larsen and Hoffmann, 2020 ; Model et al, 2020 ). For cup closure, the progressive dephosphorylation of PI(3,4,5)P3 seems to be important.…”

Section: Macropinocytosismentioning

confidence: 99%

“…Physiologically, such changes arise when cells invade anisotonic extracellular environments, e.g., the renal medulla, or following changes in intracellular osmolyte concentrations, such as during uptake or release of ions or nutrients, but also from metabolic changes, such as formation or degradation of macromolecules, e.g., proteins or glycogen. Likewise, perturbations of the double Donnan equilibrium, established by the so-called pump–leak balance ( Okada, 2004 ; Kay, 2017 ; Kay and Blaustein, 2019 ), such as changes in intracellular pH (pH i ) or inhibition of the Na + /K + -ATPase by cardiac glycosides or low temperature ( Russo et al, 2015 ), will lead to alterations of CV (for review, see Lang et al, 1998 ; Ritter et al, 2001 ; Furst et al, 2002 ; Jakab et al, 2002 ; Okada, 2004 , 2020 ; Lang, 2007 ; Hoffmann et al, 2009 ; Kunzelmann, 2015 ; Jentsch, 2016 ; Pasantes-Morales, 2016 ; De Los Heros et al, 2018 ; Delpire and Gagnon, 2018 ; Okada et al, 2019 ; Centeio et al, 2020 ; Larsen and Hoffmann, 2020 ; Model et al, 2020 ).…”

Section: Cell Volume Regulationmentioning

confidence: 99%

From Pinocytosis to Methuosis—Fluid Consumption as a Risk Factor for Cell Death

Ritter

Bresgen

Kerschbaum

2021

Front. Cell Dev. Biol.

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The volumes of a cell [cell volume (CV)] and its organelles are adjusted by osmoregulatory processes. During pinocytosis, extracellular fluid volume equivalent to its CV is incorporated within an hour and membrane area equivalent to the cell’s surface within 30 min. Since neither fluid uptake nor membrane consumption leads to swelling or shrinkage, cells must be equipped with potent volume regulatory mechanisms. Normally, cells respond to outwardly or inwardly directed osmotic gradients by a volume decrease and increase, respectively, i.e., they shrink or swell but then try to recover their CV. However, when a cell death (CD) pathway is triggered, CV persistently decreases in isotonic conditions in apoptosis and it increases in necrosis. One type of CD associated with cell swelling is due to a dysfunctional pinocytosis. Methuosis, a non-apoptotic CD phenotype, occurs when cells accumulate too much fluid by macropinocytosis. In contrast to functional pinocytosis, in methuosis, macropinosomes neither recycle nor fuse with lysosomes but with each other to form giant vacuoles, which finally cause rupture of the plasma membrane (PM). Understanding methuosis longs for the understanding of the ionic mechanisms of cell volume regulation (CVR) and vesicular volume regulation (VVR). In nascent macropinosomes, ion channels and transporters are derived from the PM. Along trafficking from the PM to the perinuclear area, the equipment of channels and transporters of the vesicle membrane changes by retrieval, addition, and recycling from and back to the PM, causing profound changes in vesicular ion concentrations, acidification, and—most importantly—shrinkage of the macropinosome, which is indispensable for its proper targeting and cargo processing. In this review, we discuss ion and water transport mechanisms with respect to CVR and VVR and with special emphasis on pinocytosis and methuosis. We describe various aspects of the complex mutual interplay between extracellular and intracellular ions and ion gradients, the PM and vesicular membrane, phosphoinositides, monomeric G proteins and their targets, as well as the submembranous cytoskeleton. Our aim is to highlight important cellular mechanisms, components, and processes that may lead to methuotic CD upon their derangement.

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Volume Regulation in Epithelia

Cited by 7 publications

References 390 publications

Cation-Chloride Cotransporters, Na/K Pump, and Channels in Cell Water/Ionic Balance Regulation Under Hyperosmolar Conditions: In Silico and Experimental Studies of Opposite RVI and AVD Responses of U937 Cells to Hyperosmolar Media

Cation-Chloride Cotransporters, Na/K Pump, and Channels in Cell Water/Ionic Balance Regulation Under Hyperosmolar Conditions: In Silico and Experimental Studies of Opposite RVI and AVD Responses of U937 Cells to Hyperosmolar Media

Balance of Na+, K+, and Cl- Fluxes in an Animal Cell with Cation-Chloride Cotransporters, Na/K Pump and Channels Under Normal and Hyperosmolar Conditions: In Silico and Experimental Studies of RVI and AVD Responses of U937 cells

From Pinocytosis to Methuosis—Fluid Consumption as a Risk Factor for Cell Death

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