Physiological significance of volume-regulatory transporters

1999 ◽  
Vol 276 (5) ◽  
pp. C995-C1011 ◽  
Author(s):  
W. Charles O’Neill
Keyword(s):  
Cell Volume ◽  
Volume Regulation ◽  
Mammalian Cells ◽  
Ion Transporters ◽  
Subsequent Growth ◽  
The Past ◽  
Shrinkage And Swelling ◽  
Acute Changes

Research over the past 25 years has identified specific ion transporters and channels that are activated by acute changes in cell volume and that serve to restore steady-state volume. The mechanism by which cells sense changes in cell volume and activate the appropriate transporters remains a mystery, but recent studies are providing important clues. A curious aspect of volume regulation in mammalian cells is that it is often absent or incomplete in anisosmotic media, whereas complete volume regulation is observed with isosmotic shrinkage and swelling. The basis for this may lie in an important role of intracellular Cl− in controlling volume-regulatory transporters. This is physiologically relevant, since the principal threat to cell volume in vivo is not changes in extracellular osmolarity but rather changes in the cellular content of osmotically active molecules. Volume-regulatory transporters are also closely linked to cell growth and metabolism, producing requisite changes in cell volume that may also signal subsequent growth and metabolic events. Thus, despite the relatively constant osmolarity in mammals, volume-regulatory transporters have important roles in mammalian physiology.

scholarly journals Hydrogen, Bicarbonate, and Their Associated Exchangers in Cell Volume Regulation

2021 ◽  
Vol 9 ◽  
Author(s):  
Yizeng Li ◽  
Xiaohan Zhou ◽  
Sean X. Sun
Keyword(s):  
Ion Channels ◽  
Cell Volume ◽  
Volume Regulation ◽  
Mammalian Cells ◽  
Molecular Mechanisms ◽  
Cell Function ◽  
Water Flux ◽  
Cell Volume Regulation ◽  
Sodium Potassium ◽  
Before And After

Cells lacking a stiff cell wall, e.g., mammalian cells, must actively regulate their volume to maintain proper cell function. On the time scale that protein production is negligible, water flow in and out of the cell determines the cell volume variation. Water flux follows hydraulic and osmotic gradients; the latter is generated by various ion channels, transporters, and pumps in the cell membrane. Compared to the widely studied roles of sodium, potassium, and chloride in cell volume regulation, the effects of proton and bicarbonate are less understood. In this work, we use mathematical models to analyze how proton and bicarbonate, combined with sodium, potassium, chloride, and buffer species, regulate cell volume upon inhibition of ion channels, transporters, and pumps. The model includes several common, widely expressed ion transporters and focuses on obtaining generic outcomes. Results show that the intracellular osmolarity remains almost constant before and after cell volume change. The steady-state cell volume does not depend on water permeability. In addition, to ensure the stability of cell volume and ion concentrations, cells need to develop redundant mechanisms to maintain homeostasis, i.e., multiple ion channels or transporters are involved in the flux of the same ion species. These results provide insights for molecular mechanisms of cell volume regulation with additional implications for water-driven cell migration.

scholarly journals Modified Sawhorse Waveform for the Voltammetric Detection of Oxytocin

2022 ◽  
Author(s):  
Favian Liu ◽  
Negar Ghasem Ardabili ◽  
Izaiah Brown ◽  
Harmain Rafi ◽  
Clarice Cook ◽  
...  
Keyword(s):  
Brain Slices ◽  
Physiological Role ◽  
Peptide Hormone ◽  
Protective Effects ◽  
Fast Scan Cyclic Voltammetry ◽  
The Past ◽  
Voltammetric Detection ◽  
Carbon Fiber Microelectrodes

Abstract Carbon fiber microelectrodes (CFMEs) have been used to detect neurotransmitters and other biomolecules using fast-scan cyclic voltammetry (FSCV) for the past few decades. This technique measures neurotransmitters such as dopamine and, more recently, physiologically relevant neuropeptides. Oxytocin, a pleiotropic peptide hormone, is physiologically important for adaptation, development, reproduction, and social behavior. This neuropeptide functions as a stress-coping molecule, an anti-inflammatory agent, and serves as an antioxidant with protective effects especially during adversity or trauma. Here, we measure tyrosine using the Modified Sawhorse Waveform (MSW), enabling enhanced electrode sensitivity for the amino acid and oxytocin peptide. Applying the MSW, decreased surface fouling and enabled codetection with other monoamines. As oxytocin contains tyrosine, the MSW was also used to detect oxytocin. The sensitivity of oxytocin detection was found to be 3.99 ± 0.49 nA/µM, (n=5). Additionally, we demonstrate that applying the MSW on CFMEs allows for real time measurements of exogenously applied oxytocin on rat brain slices. These studies may serve as novel assays for oxytocin detection in a fast, sub-second timescale with possible implications for in vivo measurements and further understanding of the physiological role of oxytocin.

scholarly journals Medawar’s PostEra: Galectins Emerged as Key Players During Fetal-Maternal Glycoimmune Adaptation

2021 ◽  
Vol 12 ◽  
Author(s):  
Ellen Menkhorst ◽  
Nandor Gabor Than ◽  
Udo Jeschke ◽  
Gabriela Barrientos ◽  
Laszlo Szereday ◽  
...  
Keyword(s):  
Immune Cell ◽  
Successful Pregnancy ◽  
Fetal Health ◽  
The Past ◽  
Mammalian Embryogenesis ◽  
Carbohydrate Ligands ◽  
Membrane Bound

Lectin-glycan interactions, in particular those mediated by the galectin family, regulate many processes required for a successful pregnancy. Over the past decades, increasing evidence gathered from in vitro and in vivo experiments indicate that members of the galectin family specifically bind to both intracellular and membrane bound carbohydrate ligands regulating angiogenesis, immune-cell adaptations required to tolerate the fetal semi-allograft and mammalian embryogenesis. Therefore, galectins play important roles in fetal development and placentation contributing to maternal and fetal health. This review discusses the expression and role of galectins during the course of pregnancy, with an emphasis on maternal immune adaptions and galectin-glycan interactions uncovered in the recent years. In addition, we summarize the galectin fingerprints associated with pathological gestation with particular focus on preeclampsia.

Effect of hemorrhagic shock on hepatic transmembrane potentials and intracellular electrolytes, in vivo

1981 ◽  
Vol 240 (3) ◽  
pp. R211-R219 ◽  
Author(s):  
M. M. Sayeed ◽  
R. J. Adler ◽  
I. H. Chaudry ◽  
A. E. Baue
Keyword(s):  
Hemorrhagic Shock ◽  
Cell Volume ◽  
Volume Regulation ◽  
Cell Volume Regulation ◽  
Shed Blood ◽  
Average Value ◽  
Transmembrane Potentials ◽  
Relative Membrane Permeability

In this study we investigated in vivo changes in hepatic cellular electrolytes and resting transmembrane potentials (Em) during hemorrhagic shock. Hepatic Na-K transport and cell volume regulation were assessed in vitro. Rats were bled and the ensuing hypotension (40 mmHg) was maintained by returning 25-30% (intermediate-shock, IS) or 55-60% (late-shock, LS) of the shed blood. We resuscitated IS rats by reinfusion of all of the remaining shed blood and Ringer's lactate solution. Hepatic cellular Na and Cl increased and K decreased progressively with shock. Resuscitation of IS rats restored cell K and Cl but not Na to preshock levels. Em decreased from the control average value of -40 (mV) to -31 in IS and -19 in LS. Em was partially restored (-36 mV) after resuscitation. We evaluated changes in relative membrane permeability to Na and K (PNa/PK) with shock by assuming Em either to be a Na-K exchange diffusion potential or due to an unequally coupled movement of Na and K. These evaluations show a lack of effect of shock (IS, with or without resuscitation) on PNa/PK. Our observations are compatible with failure of an electrogenic Na pump in shock. This may be related to loss of hepatic cell volume regulation in shock.

Hemorrhagic shock impairs myocardial cell volume regulation and membrane integrity in dogs

1987 ◽  
Vol 252 (6) ◽  
pp. H1203-H1210
Author(s):  
J. W. Horton
Keyword(s):  
Hemorrhagic Shock ◽  
Cell Volume ◽  
Volume Regulation ◽  
Membrane Integrity ◽  
Cell Volume Regulation ◽  
Calcium Entry ◽  
Tissue Water ◽  
Total Tissue

An in vitro myocardial slice technique was used to quantitate alterations in cell volume regulation and membrane integrity after 2 h of hemorrhagic shock. After in vitro incubation in Krebs-Ringer-phosphate medium containing trace [14C]inulin, values (ml H2O/g dry wt) for control nonshocked myocardial slices were 4.03 +/- 0.11 (SE) for total water, 2.16 +/- 0.07 for inulin impermeable space, and 1.76 +/- 0.15 for inulin diffusible space. Shocked myocardial slices showed impaired response to cold incubation (0 degrees C, 60 min). After 2 h of in vivo shock, total tissue water, inulin diffusible space, and inulin impermeable space increased significantly (+19.2 +/- 2.4, +8.1 +/- 1.9, +34.4 +/- 6.1%, respectively) for subendocardium, whereas changes in subepicardium parameters were minimal. Shock-induced cellular swelling was accompanied by an increased total tissue sodium, but no change in tissue potassium. Calcium entry blockade in vivo (lidoflazine, 20 micrograms X kg-1 X min-1 during the last 60 min of shock) significantly reduced subendocardial total tissue water as compared with shock-untreated dogs. In addition, calcium entry blockade reduced shock-induced increases in inulin impermeable space and inulin diffusible space. In vitro myocardial slice studies confirm alterations in subendocardial membrane integrity after 2 h of in vivo hemorrhagic shock. Shock-induced abnormalities in myocardial cell volume regulation are reduced by calcium entry blockade in vivo.

Modeling cell volume regulation in nonexcitable cells: the roles of the Na+ pump and of cotransport systems

1998 ◽  
Vol 275 (4) ◽  
pp. C1067-C1080 ◽  
Author(s):  
Julio A. Hernández ◽  
Ernesto Cristina
Keyword(s):  
Cell Volume ◽  
Volume Regulation ◽  
Present Model ◽  
Animal Cell ◽  
Cell Volume Regulation ◽  
Kinetic Scheme ◽  
Short Term ◽  
Rates Of Change

The purpose of this study is to contribute to understanding the role of Na+-K+-ATPase and of ionic cotransporters in the regulation of cell volume, by employing a model that describes the rates of change of the intracellular concentrations of Na+, K+, and Cl−, of the cell volume, and of the membrane potential. In most previous models of dynamic cellular phenomena, Na+-K+-ATPase is incorporated via phenomenological formulations; the enzyme is incorporated here via an explicit kinetic scheme. Another feature of the present model is the capability to perform short-term cell volume regulation mediated by cotransporters of KCl and NaCl. The model is employed to perform numerical simulations for a “typical” nonpolarized animal cell. Basically, the results are consistent with the view that the Na+ pump mainly plays a long-term role in the maintenance of the electrochemical gradients of Na+ and K+ and that short-term cell volume regulation is achieved via passive transport, exemplified in this case by the cotransport of KCl and NaCl.

scholarly journals Functional genetic encoding of sulfotyrosine in mammalian cells

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Xinyuan He ◽  
Yan Chen ◽  
Daisy Guiza Beltran ◽  
Maia Kelly ◽  
Bin Ma ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Biochemical Characterization ◽  
Trna Synthetase ◽  
Functional Verification ◽  
Cellular Processes ◽  
Genetic Encoding ◽  
Efficient Expression

Abstract Protein tyrosine O-sulfation (PTS) plays a crucial role in extracellular biomolecular interactions that dictate various cellular processes. It also involves in the development of many human diseases. Regardless of recent progress, our current understanding of PTS is still in its infancy. To promote and facilitate relevant studies, a generally applicable method is needed to enable efficient expression of sulfoproteins with defined sulfation sites in live mammalian cells. Here we report the engineering, in vitro biochemical characterization, structural study, and in vivo functional verification of a tyrosyl-tRNA synthetase mutant for the genetic encoding of sulfotyrosine in mammalian cells. We further apply this chemical biology tool to cell-based studies on the role of a sulfation site in the activation of chemokine receptor CXCR4 by its ligand. Our work will not only facilitate cellular studies of PTS, but also paves the way for economical production of sulfated proteins as therapeutic agents in mammalian systems.

scholarly journals Dynamic measurement of cytosolic pH and [NO3−] uncovers the role of the vacuolar transporter AtCLCa in cytosolic pH homeostasis

2020 ◽  
Vol 117 (26) ◽  
pp. 15343-15353 ◽  
Author(s):  
Elsa Demes ◽  
Laetitia Besse ◽  
Paloma Cubero-Font ◽  
Béatrice Satiat-Jeunemaitre ◽  
Sébastien Thomine ◽  
...  
Keyword(s):  
Chloride Channel ◽  
Loss Of Function ◽  
Ion Transporters ◽  
Ph Homeostasis ◽  
Cytosolic Ph ◽  
Cellular Processes ◽  
Plasma Membrane Proton Pump ◽  
Cytosolic Acidification

Ion transporters are key players of cellular processes. The mechanistic properties of ion transporters have been well elucidated by biophysical methods. Meanwhile, the understanding of their exact functions in cellular homeostasis is limited by the difficulty of monitoring their activity in vivo. The development of biosensors to track subtle changes in intracellular parameters provides invaluable tools to tackle this challenging issue. AtCLCa (Arabidopsis thalianaChloride Channel a) is a vacuolar NO3−/H+exchanger regulating stomata aperture inA.thaliana. Here, we used a genetically encoded biosensor, ClopHensor, reporting the dynamics of cytosolic anion concentration and pH to monitor the activity of AtCLCa in vivo inArabidopsisguard cells. We first found that ClopHensor is not only a Cl−but also, an NO3−sensor. We were then able to quantify the variations of NO3−and pH in the cytosol. Our data showed that AtCLCa activity modifies cytosolic pH and NO3−. In an AtCLCa loss of function mutant, the cytosolic acidification triggered by extracellular NO3−and the recovery of pH upon treatment with fusicoccin (a fungal toxin that activates the plasma membrane proton pump) are impaired, demonstrating that the transport activity of this vacuolar exchanger has a profound impact on cytosolic homeostasis. This opens a perspective on the function of intracellular transporters of the Chloride Channel (CLC) family in eukaryotes: not only controlling the intraorganelle lumen but also, actively modifying cytosolic conditions.

Cell volume regulation by skate erythrocytes: role of potassium

1990 ◽  
Vol 258 (5) ◽  
pp. R1217-R1223 ◽  
Author(s):  
K. G. Dickman ◽  
L. Goldstein
Keyword(s):  
Cell Volume ◽  
Phorbol Ester ◽  
Volume Regulation ◽  
Regulatory Volume Decrease ◽  
Cell Volume Regulation ◽  
Disulfonic Acid ◽  
Ionophore A23187 ◽  
K Uptake ◽  
K Transport

The role of K transport during cell volume regulation in response to extracellular osmolality, protein kinase C activation, and cellular Ca was examined in skate (Raja erinacea) red blood cells (RBC). Reduction of medium osmolality from 960 to 660 mosmol/kgH2O had no effect on K uptake or efflux despite a 25% increase in cell volume. Further reduction to 460 mosmol/kgH2O caused K uptake to double and K efflux to triple resulting in net K loss. Net K efflux in 460 mosmol/kgH2O medium was correlated with the presence of a regulatory volume decrease, which was sensitive to the anion transport inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) and insensitive to chloride replacement. K-K exchange was absent in both isotonic and hypotonic media. Treatment with the Ca ionophore A23187 in the presence of Ca had no effect on either cell volume or K efflux in isotonic medium, indicating the absence of Ca-activated K transport. In contrast, phorbol ester treatment caused cell volume, Na content, and proton and K efflux to increase. Consistent with activation of Na-H exchange, phorbol ester effects were inhibited by dimethylamiloride. This study constitutes the first demonstration of volume-sensitive K transport in RBC from the most primitive vertebrate studied to date.

Role of concentration and size of intracellular macromolecules in cell volume regulation

1997 ◽  
Vol 273 (2) ◽  
pp. C360-C370 ◽  
Author(s):  
J. C. Summers ◽  
L. Trais ◽  
R. Lajvardi ◽  
D. Hergan ◽  
R. Buechler ◽  
...  
Keyword(s):  
Cell Volume ◽  
Volume Regulation ◽  
Regulatory Volume Decrease ◽  
Cell Volume Regulation ◽  
Molecular Physiology ◽  
Average Molecular Mass ◽  
Membrane Stretch ◽  
Ca2 Channels ◽  
Volume Decrease

To gain insight into the mechanism(s) by which cells sense volume changes, specific predictions of the macromolecular crowding theory (A. P. Minton. In: Cellular and Molecular Physiology of Cell Volume Regulation, edited by K. Strange. Boca Raton, FL: CRC, 1994, p. 181-190. A. P. Minton, C. C. Colclasure, and J. C. Parker. Proc. Natl. Acad. Sci. USA 89: 10504-10506, 1992) were tested on the volume of internally perfused barnacle muscle cells. This preparation was chosen because it allows assessment of the effect on cell volume of changes in the intracellular macromolecular concentration and size while maintaining constant the ionic strength, membrane stretch, and osmolality. The predictions tested were that isotonic replacement of large macromolecules by smaller ones should induce volume decreases proportional to the initial macromolecular concentration and size as well as to the magnitude of the concentration reduction. The experimental results were consistent with these predictions: isotonic replacement of proteins or polymers with sucrose induced volume reductions, but this effect was only observed when the replacement was > or = 25% and the particular macromolecule had an average molecular mass of < or = 20 kDa and a concentration of at least 18 mg/ml. Volume reduction was effected by a mechanism identical with that of hypotonicity-induced regulatory volume decrease, namely, activation of verapamil-sensitive Ca2+ channels.

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