scholarly journals Aquaporin-4–dependent K+ and water transport modeled in brain extracellular space following neuroexcitation

2012 ◽  
Vol 141 (1) ◽  
pp. 119-132 ◽  
Author(s):  
Byung-Ju Jin ◽  
Hua Zhang ◽  
Devin K. Binder ◽  
A.S. Verkman
Keyword(s):  
Water Transport ◽  
Water Permeability ◽  
Extracellular Space ◽  
Water Channel ◽  
Aquaporin 4 ◽  
Solute Diffusion ◽  
Water Transport Properties ◽  
And Diffusion ◽  
K Permeability ◽  
Brain Extracellular Space

Potassium (K+) ions released into brain extracellular space (ECS) during neuroexcitation are efficiently taken up by astrocytes. Deletion of astrocyte water channel aquaporin-4 (AQP4) in mice alters neuroexcitation by reducing ECS [K+] accumulation and slowing K+ reuptake. These effects could involve AQP4-dependent: (a) K+ permeability, (b) resting ECS volume, (c) ECS contraction during K+ reuptake, and (d) diffusion-limited water/K+ transport coupling. To investigate the role of these mechanisms, we compared experimental data to predictions of a model of K+ and water uptake into astrocytes after neuronal release of K+ into the ECS. The model computed the kinetics of ECS [K+] and volume, with input parameters including initial ECS volume, astrocyte K+ conductance and water permeability, and diffusion in astrocyte cytoplasm. Numerical methods were developed to compute transport and diffusion for a nonstationary astrocyte–ECS interface. The modeling showed that mechanisms b–d, together, can predict experimentally observed impairment in K+ reuptake from the ECS in AQP4 deficiency, as well as altered K+ accumulation in the ECS after neuroexcitation, provided that astrocyte water permeability is sufficiently reduced in AQP4 deficiency and that solute diffusion in astrocyte cytoplasm is sufficiently low. The modeling thus provides a potential explanation for AQP4-dependent K+/water coupling in the ECS without requiring AQP4-dependent astrocyte K+ permeability. Our model links the physical and ion/water transport properties of brain cells with the dynamics of neuroexcitation, and supports the conclusion that reduced AQP4-dependent water transport is responsible for defective neuroexcitation in AQP4 deficiency.

scholarly journals Spatial model of convective solute transport in brain extracellular space does not support a “glymphatic” mechanism

2016 ◽  
Vol 148 (6) ◽  
pp. 489-501 ◽  
Author(s):  
Byung-Ju Jin ◽  
Alex J. Smith ◽  
Alan S. Verkman
Keyword(s):  
Solute Transport ◽  
Water Permeability ◽  
Extracellular Space ◽  
Fluid Transport ◽  
Volume Fraction ◽  
Convective Transport ◽  
Solute Diffusion ◽  
Model Parameters ◽  
Pulsatile Pressure ◽  
Brain Extracellular Space

A “glymphatic system,” which involves convective fluid transport from para-arterial to paravenous cerebrospinal fluid through brain extracellular space (ECS), has been proposed to account for solute clearance in brain, and aquaporin-4 water channels in astrocyte endfeet may have a role in this process. Here, we investigate the major predictions of the glymphatic mechanism by modeling diffusive and convective transport in brain ECS and by solving the Navier–Stokes and convection–diffusion equations, using realistic ECS geometry for short-range transport between para-arterial and paravenous spaces. Major model parameters include para-arterial and paravenous pressures, ECS volume fraction, solute diffusion coefficient, and astrocyte foot-process water permeability. The model predicts solute accumulation and clearance from the ECS after a step change in solute concentration in para-arterial fluid. The principal and robust conclusions of the model are as follows: (a) significant convective transport requires a sustained pressure difference of several mmHg between the para-arterial and paravenous fluid and is not affected by pulsatile pressure fluctuations; (b) astrocyte endfoot water permeability does not substantially alter the rate of convective transport in ECS as the resistance to flow across endfeet is far greater than in the gaps surrounding them; and (c) diffusion (without convection) in the ECS is adequate to account for experimental transport studies in brain parenchyma. Therefore, our modeling results do not support a physiologically important role for local parenchymal convective flow in solute transport through brain ECS.

scholarly journals Relative importance of geometrical and intrinsic water transport properties of active layers in the water permeability of polyamide thin-film composite membranes

2018 ◽  
Vol 564 ◽  
pp. 935-944 ◽  
Author(s):  
Lin Lin ◽  
Timothy M. Weigand ◽  
Matthew W. Farthing ◽  
Panitan Jutaporn ◽  
Cass T. Miller ◽  
...  
Keyword(s):  
Thin Film ◽  
Transport Properties ◽  
Water Transport ◽  
Water Permeability ◽  
Composite Membranes ◽  
Relative Importance ◽  
Film Composite ◽  
Thin Film Composite ◽  
Active Layers ◽  
Water Transport Properties

scholarly journals Water Transport and Ion Diffusion Investigation of an Amphotericin B-Based Channel Applied to Forward Osmosis: A Simulation Study

Membranes ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 646
Author(s):  
Hao-Chen Wu ◽  
Tomohisa Yoshioka ◽  
Keizo Nakagawa ◽  
Takuji Shintani ◽  
Hideto Matsuyama
Keyword(s):  
Amphotericin B ◽  
Water Transport ◽  
Water Permeability ◽  
Salt Water ◽  
Water Channel ◽  
Forward Osmosis ◽  
Water Molecules ◽  
Ion Leakage ◽  
Channel Models ◽  
Water Permeation

The use of an Amphotericin B_Ergosterol (AmBEr) channel as an artificial water channel in forward osmosis filtration (FO) was studied via molecular dynamics (MD) simulation. Three channel models were constructed: a common AmBEr channel and two modified C3deOAmB_Ergosterol (C3deOAmBEr) channels with different diameters (12 Å and 18 Å). During FO filtration simulation, the osmotic pressure of salt-water was a driving force for water permeation. We examined the effect of the modified C3deOAmBEr channel on the water transport performance. By tracing the change of the number of water molecules along with simulation time in the saltwater region, the water permeability of the channel models could be calculated. A higher water permeability was observed for a modified C3deOAmBEr channel, and there was no ion permeation during the entire simulation period. The hydrated ions and water molecules were placed into the channel to explore the ion leakage behavior of the channels. The mean squared displacement (MSD) of ions and water molecules was obtained to study the ion leakage performance. The Amphotericin B-based channels showed excellent selectivity of water molecules against ions. The results obtained on an atomistic scale could assist in determining the properties and the optimal filtration applications for Amphotericin B-based channels.

scholarly journals Quantitative Measurement of Diffusion-weighted Imaging Signal Using Expression-controlled Aquaporin-4 Cells: Comparative Study of 2-compartment and Diffusion Kurtosis Imaging Models

2021 ◽  
Author(s):  
Akiko Imaizumi ◽  
Takayuki Obata ◽  
Jeff Kershaw ◽  
Yasuhiko Tachibana ◽  
Yoichiro Abe ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Water Permeability ◽  
Diffusion Weighted Imaging ◽  
Aquaporin 4 ◽  
Diffusion Kurtosis Imaging ◽  
Parameter Estimates ◽  
Aqp4 Expression ◽  
Diffusion Weighted ◽  
Diffusion Kurtosis ◽  
And Diffusion

Purpose: The purpose of this study was to compare parameter estimates for the 2-compartment (2Comp) and diffusion kurtosis imaging (DKm) models obtained from diffusion-weighted imaging (DWI) of aquaporin-4 (AQP4) expression-controlled cells, and to look for biomarkers that indicate differences in the cell membrane water permeability. Methods: DWI was performed on AQP4-expressing and non-expressing cells and the signal was analyzed with the 2Comp and DKm models. For the 2Comp model, the diffusion coefficients (Df, Ds) and volume fractions (Ff, Fs, Ff=1-Fs) of the fast and slow compartments were estimated. For the DKm model, estimates of the diffusion kurtosis (K) and corrected diffusion coefficient (D) were obtained. Results: For the 2Comp model, Ds and Fs showed clear differences between AQP4-expressing and non-expressing cells. Fs was also sensitive to cell density. There was no clear relationship with the cell type for the DKm parameters. Conclusions: Changes to cell membrane water permeability due to AQP4 expression affected DWI of cell suspensions. For the 2Comp and DKm models, Ds was the parameter most sensitive to differences in AQP4 expression.

scholarly journals Synucleinopathy alters nanoscale organization and diffusion in the brain extracellular space through hyaluronan remodeling

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Federico N. Soria ◽  
Chiara Paviolo ◽  
Evelyne Doudnikoff ◽  
Marie-Laure Arotcarena ◽  
Antony Lee ◽  
...  
Keyword(s):  
Extracellular Space ◽  
The Brain ◽  
And Diffusion ◽  
Brain Extracellular Space

scholarly journals A novel human aquaporin-4 splice variant exhibits a dominant-negative activity: a new mechanism to regulate water permeability

2014 ◽  
Vol 25 (4) ◽  
pp. 470-480 ◽  
Author(s):  
Manuela De Bellis ◽  
Francesco Pisani ◽  
Maria Grazia Mola ◽  
Davide Basco ◽  
Francesco Catalano ◽  
...  
Keyword(s):  
Water Transport ◽  
Skeletal Muscles ◽  
Water Channel ◽  
Surface Expression ◽  
Dominant Negative ◽  
Aquaporin 4 ◽  
Cell Surface Expression ◽  
Dominant Negative Effect ◽  
Negative Effect ◽  
Dominant Negative Activity

Two major isoforms of aquaporin-4 (AQP4) have been described in human tissue. Here we report the identification and functional analysis of an alternatively spliced transcript of human AQP4, AQP4-Δ4, that lacks exon 4. In transfected cells AQP4-Δ4 is mainly retained in the endoplasmic reticulum and shows no water transport properties. When AQP4-Δ4 is transfected into cells stably expressing functional AQP4, the surface expression of the full-length protein is reduced. Furthermore, the water transport activity of the cotransfectants is diminished in comparison to transfectants expressing only AQP4. The observed down-regulation of both the expression and water channel activity of AQP4 is likely to originate from a dominant-negative effect caused by heterodimerization between AQP4 and AQP4-Δ4, which was detected in coimmunoprecipitation studies. In skeletal muscles, AQP4-Δ4 mRNA expression inversely correlates with the level of AQP4 protein and is physiologically associated with different types of skeletal muscles. The expression of AQP4-Δ4 may represent a new regulatory mechanism through which the cell-surface expression and therefore the activity of AQP4 can be physiologically modulated.

The role of aquaporin-4 in cerebral water transport and edema

2007 ◽  
Vol 22 (5) ◽  
pp. 1-7 ◽  
Author(s):  
Orin Bloch ◽  
Geoffrey T. Manley
Keyword(s):  
Water Transport ◽  
Cerebral Edema ◽  
Vasogenic Edema ◽  
Water Channel ◽  
Brain Parenchyma ◽  
Aquaporin 4 ◽  
Molecular Water ◽  
Altered Expression ◽  
Cellular Water ◽  
The Brain

✓Despite decades of research into the pathogenesis of cerebral edema, nonsurgical therapy for brain swelling has advanced very little after more than half a century. Recent advancements in our understanding of molecular water transport have generated interest in new targets for edema therapy. Aquaporin-4 (AQP4) is the primary cellular water channel in the brain, localized to astrocytic foot processes along the blood–brain barrier and brain–cerebrospinal fluid interface. Multiple studies of transgenic mice with a complete deficiency or altered expression of AQP4 suggest a prominent role for AQP4 in cerebral water transport. In models of cellular (cytotoxic) edema, AQP4 deletion or alteration has been shown to be protective, reducing edema burden and improving overall survival. In contrast, AQP4 deletion in extra-cellular (vasogenic) edema results in decreased edema clearance and greater progression of disease. The data strongly support the conclusion that AQP4 plays a pivotal role in cerebral water transport and is an essential mediator in the formation and resorption of edema fluid from the brain parenchyma. These findings also suggest that drug therapy targeting AQP4 function and expression may dramatically alter our ability to treat cerebral edema.

Imidazole derivatives as artificial water channel building-blocks: structural design influence on water permeability

2018 ◽  
Vol 209 ◽  
pp. 113-124 ◽  
Author(s):  
Zhanhu Sun ◽  
Istvan Kocsis ◽  
Yuhao Li ◽  
Yves-Marie Legrand ◽  
Mihail Barboiu
Keyword(s):  
Water Transport ◽  
Water Permeability ◽  
Structural Design ◽  
Water Channel ◽  
Building Blocks ◽  
Structural Modifications ◽  
Imidazole Derivatives ◽  
Permeability Variation ◽  
Self Assembled ◽  
Artificial Water

A series of mono- and di-ureidoethylimidazole derivatives were tested as self-assembled supramolecular channels for water transport across a vesicle bilayer. Structural modifications of the selected compounds were related to permeability variation.

Water permeability of aquaporin-4 is decreased by protein kinase C and dopamine

2002 ◽  
Vol 283 (2) ◽  
pp. F309-F318 ◽  
Author(s):  
Marina Zelenina ◽  
Sergey Zelenin ◽  
Alexander A. Bondar ◽  
Hjalmar Brismar ◽  
Anita Aperia
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Water Permeability ◽  
Fluorescent Protein ◽  
Collecting Duct ◽  
Basolateral Membrane ◽  
Water Channel ◽  
Aquaporin 4 ◽  
Transfected Cells ◽  
Kinase C

Aquaporin-4 (AQP4) plays an important role in the basolateral movement of water in the collecting duct. Here we show that this water channel can be dynamically regulated. Water permeability ( P f) was measured in individual LLC-PK1 cells that were transiently transfected with AQP4. To identify which cells were transfected, AQP4 was tagged at the NH2 terminus with green fluorescent protein. Transfected cells showed a strong fluorescent signal in basolateral membrane and a low-to-negligible signal in the cytosol and apical membrane. Activation of protein kinase C (PKC) with phorbol 12,13-dibutyrate (PDBu) significantly decreased P f of cells expressing AQP4 but had no effect on neighboring untransfected cells. No redistribution of AQP4 in response to PDBu was detected. Dopamine also decreased the P f in transfected cells. The effect was abolished by the PKC inhibitor Ro 31–8220. Reduction of AQP4 water permeability by PDBu and dopamine was abolished by point mutation of Ser180, a consensus site for PKC phosphorylation. We conclude that PKC and dopamine decrease AQP4 water permeability via phosphorylation at Ser180 and that the effect is likely mediated by gating of the channel.

scholarly journals The Water Channel Aquaporin-8 Is Mainly Intracellular in Rat Hepatocytes, and Its Plasma Membrane Insertion Is Stimulated by Cyclic AMP

2001 ◽  
Vol 276 (15) ◽  
pp. 12147-12152 ◽  
Author(s):  
Fabiana Garcı́a ◽  
Arlinet Kierbel ◽  
M. Cecilia Larocca ◽  
Sergio A. Gradilone ◽  
Patrick Splinter ◽  
...  
Keyword(s):  
Water Transport ◽  
Water Permeability ◽  
Plasma Membranes ◽  
Water Channel ◽  
Rat Hepatocytes ◽  
Immunoblot Analysis ◽  
Subcellular Fractionation ◽  
Bile Secretion ◽  
Confocal Immunofluorescence Microscopy ◽  
Microsomal Membranes

We previously found that water transport across hepatocyte plasma membranes occurs mainly via a non-channel mediated pathway. Recently, it has been reported that mRNA for the water channel, aquaporin-8 (AQP8), is present in hepatocytes. To further explore this issue, we studied protein expression, subcellular localization, and regulation of AQP8 in rat hepatocytes. By subcellular fractionation and immunoblot analysis, we detected anN-glycosylated band of ∼34 kDa corresponding to AQP8 in hepatocyte plasma and intracellular microsomal membranes. Confocal immunofluorescence microscopy for AQP8 in cultured hepatocytes showed a predominant intracellular vesicular localization. Dibutyryl cAMP (Bt2cAMP) stimulated the redistribution of AQP8 to plasma membranes. Bt2cAMP also significantly increased hepatocyte membrane water permeability, an effect that was prevented by the water channel blocker dimethyl sulfoxide. The microtubule blocker colchicine but not its inactive analog lumicolchicine inhibited the Bt2cAMP effect on both AQP8 redistribution to cell surface and hepatocyte membrane water permeability. Our data suggest that in rat hepatocytes AQP8 is localized largely in intracellular vesicles and can be redistributed to plasma membranes via a microtubule-depending, cAMP-stimulated mechanism. These studies also suggest that aquaporins contribute to water transport in cAMP-stimulated hepatocytes, a process that could be relevant to regulated hepatocyte bile secretion.

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