scholarly journals Targeting the Trafficking of Kidney Water Channels for Therapeutic Benefit

2020 ◽  
Vol 60 (1) ◽  
pp. 175-194 ◽  
Author(s):  
Pui W. Cheung ◽  
Richard Bouley ◽  
Dennis Brown
Keyword(s):  
Lipid Bilayers ◽  
Water Movement ◽  
Water Channel ◽  
Plasma Osmolality ◽  
Water Channels ◽  
Therapeutic Benefit ◽  
Body Volume ◽  
Pka Pathway ◽  
Complex Signaling ◽  
Urine Concentrating Ability

The ability to regulate water movement is vital for the survival of cells and organisms. In addition to passively crossing lipid bilayers by diffusion, water transport is also driven across cell membranes by osmotic gradients through aquaporin water channels. There are 13 aquaporins in human tissues, and of these, aquaporin-2 (AQP2) is the most highly regulated water channel in the kidney: The expression and trafficking of AQP2 respond to body volume status and plasma osmolality via the antidiuretic hormone, vasopressin (VP). Dysfunctional VP signaling in renal epithelial cells contributes to disorders of water balance, and research initially focused on regulating the major cAMP/PKA pathway to normalize urine concentrating ability. With the discovery of novel and more complex signaling networks that regulate AQP2 trafficking, promising therapeutic targets have since been identified. Several strategies based on data from preclinical studies may ultimately translate to the care of patients with defective water homeostasis.

Urine concentrating defect in prostaglandin EP1-deficient mice

2007 ◽  
Vol 292 (2) ◽  
pp. F868-F875 ◽  
Author(s):  
Chris R. J. Kennedy ◽  
Huaqi Xiong ◽  
Sherine Rahal ◽  
Jacqueline Vanderluit ◽  
Ruth S. Slack ◽  
...  
Keyword(s):  
Collecting Duct ◽  
Water Channel ◽  
Significant Proportion ◽  
Plasma Osmolality ◽  
Urine Osmolality ◽  
Urine Concentration ◽  
Prostaglandin E ◽  
Rt Pcr ◽  
Urine Concentrating Ability

We investigated the role of the prostaglandin E2 (PGE2) EP1 receptor in modulating urine concentration as it is expressed along the renal collecting duct where arginine-vasopressin (AVP) exerts its anti-diuretic activity, and in the paraventricular and supraoptic nuclei of the hypothalamus where AVP is synthesized. The urine osmolality of EP1-null mice (EP1−/−) failed to match levels achieved by wild-type (WT) counterparts upon water deprivation (WD) for 24 h. This difference was reflected by higher plasma osmolality in WD EP1−/− mice. Along the collecting duct, the induction and subapical to plasma membrane translocation of the aquaporin-2 water channel in WD EP1−/− mice appeared equivalent to that of WD WT mice as determined by quantitative RT-PCR and immunohistochemistry. However, medullary interstitial osmolalities dropped significantly in EP1−/− mice following WD. Furthermore, urinary AVP levels of WD EP1−/− mice were significantly lower than those of WD WT mice. This deficit could be traced back to a blunted induction of hypothalamic AVP mRNA expression in WD EP1−/− mice as determined by quantitative RT-PCR. Administration of the AVP mimetic [deamino-Cys1,d-Arg8]-vasopressin restored a significant proportion of the urine concentrating ability of WD EP1−/− mice. When mice were water loaded to suppress endogenous AVP production, urine osmolalities increased equally for WT and EP1−/− mice. These data suggest that PGE2 modulates urine concentration by acting at EP1 receptors, not in the collecting duct, but within the hypothalamus to promote AVP synthesis in response to acute WD.

scholarly journals The energetic barrier to single-file water flow through narrow channels

2021 ◽  
Author(s):  
Juergen Pfeffermann ◽  
Nikolaus Goessweiner-Mohr ◽  
Peter Pohl
Keyword(s):  
Lipid Bilayers ◽  
Degrees Of Freedom ◽  
Water Channel ◽  
Water Channels ◽  
Bulk Water ◽  
State Theory ◽  
Narrow Channels ◽  
Biological Water ◽  
Free Energy Of Activation ◽  
Single File

AbstractVarious nanoscopic channels of roughly equal diameter and length facilitate single-file diffusion at vastly different rates. The underlying variance of the energetic barriers to transport is poorly understood. First, water partitioning into channels so narrow that individual molecules cannot overtake each other incurs an energetic penalty. Corresponding estimates vary widely depending on how the sacrifice of two out of four hydrogen bonds is accounted for. Second, entropy differences between luminal and bulk water may arise: additional degrees of freedom caused by dangling OH-bonds increase entropy. At the same time, long-range dipolar water interactions decrease entropy. Here, we dissect different contributions to Gibbs free energy of activation, ΔG‡, for single-file water transport through narrow channels by analyzing experimental results from water permeability measurements on both bare lipid bilayers and biological water channels that (i) consider unstirred layer effects and (ii) adequately count the channels in reconstitution experiments. First, the functional relationship between water permeabilities and Arrhenius activation energies indicates negligible differences between the entropies of intraluminal water and bulk water. Second, we calculate ΔG‡ from unitary water channel permeabilities using transition state theory. Plotting ΔG‡ as a function of the number of H-bond donating or accepting pore-lining residues results in a 0.1 kcal/mol contribution per residue. The resulting upper limit for partial water dehydration amounts to 2 kcal/mol. In the framework of biomimicry, our analysis provides valuable insights for the design of synthetic water channels. It thus may aid in the urgent endeavor towards combating global water scarcity.

Radio and Electrical Measurements on Glacial Streams

1987 ◽  
Vol 33 (114) ◽  
pp. 239-242
Author(s):  
M. E. R. Walford
Keyword(s):  
Electrical Conductivity ◽  
Water Channel ◽  
Water System ◽  
Low Frequency ◽  
Water Channels ◽  
Radiative Loss ◽  
Radio Waves ◽  
Electrical Measurements ◽  
Water Conductivity ◽  
Glacier Surface

AbstractWe discuss the suggestion that small underwater transmitters might be used to illuminate the interior of major englacial water channels with radio waves. Once launched, the radio waves would naturally tend to be guided along the channels until attenuated by absorption and by radiative loss. Receivers placed within the channels or at the glacier surface could be used to detect the signals. They would provide valuable information about the connectivity of the water system. The electrical conductivity of the water is of crucial importance. A surface stream on Storglaciären, in Sweden, was found, using a low-frequency technique, to have a conductivity of approximately 4 × 10−4 S m−1. Although this is several hundred times higher than the conductivity of the surrounding glacier ice, the contrast is not sufficient to permit us simply to use electrical conductivity measurements to establish the connectivity of englacial water channels. However, the water conductivity is sufficiently small that, under favourable circumstances, radio signals should be detectable after travelling as much as a few hundred metres along an englacial water channel. In a preliminary field experiment, we demonstrated semi quantitatively that radio waves do indeed propagate as expected, at least in surface streams. We conclude that under-water radio transmitters could be of real practical value in the study of the englacial water system, provided that sufficiently robust devices can be constructed. In a subglacial channel, however, we expect the radio range would be much smaller, the environment much harsher, and the technique of less practical value.

scholarly journals Urea and NaCl regulate UT-A1 urea transporter in opposing directions via TonEBP pathway during osmotic diuresis

2009 ◽  
Vol 296 (1) ◽  
pp. F67-F77 ◽  
Author(s):  
Yu-Mi Kim ◽  
Wan-Young Kim ◽  
Hyun-Wook Lee ◽  
Jin Kim ◽  
H. Moo Kwon ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Plasma Osmolality ◽  
Urea Concentration ◽  
Urea Transporter ◽  
Osmotic Diuresis ◽  
High Salt Diet ◽  
Salt Diet ◽  
Low Protein ◽  
Low Salt ◽  
Urine Concentrating Ability

In our previous studies of varying osmotic diuresis, UT-A1 urea transporter increased when urine and inner medullary (IM) interstitial urea concentration decreased. The purposes of this study were to examine 1) whether IM interstitial tonicity changes with different urine urea concentrations during osmotic dieresis and 2) whether the same result occurs even if the total urinary solute is decreased. Rats were fed a 4% high-salt diet (HSD) or a 5% high-urea diet (HUD) for 2 wk and compared with the control rats fed a regular diet containing 1% NaCl. The urine urea concentration decreased in HSD but increased in HUD. In the IM, UT-A1 and UT-A3 urea transporters, CLC-K1 chloride channel, and tonicity-enhanced binding protein (TonEBP) transcription factor were all increased in HSD and decreased in HUD. Next, rats were fed an 8% low-protein diet (LPD) or a 0.4% low-salt diet (LSD) to decrease the total urinary solute. Urine urea concentration significantly decreased in LPD but significantly increased in LSD. Rats fed the LPD had increased UT-A1 and UT-A3 in the IM base but decreased in the IM tip, resulting in impaired urine concentrating ability. The LSD rats had decreased UT-A1 and UT-A3 in both portions of the IM. CLC-K1 and TonEBP were unchanged by LPD or LSD. We conclude that changes in CLC-K1, UT-A1, UT-A3, and TonEBP play important roles in the renal response to osmotic diuresis in an attempt to minimize changes in plasma osmolality and maintain water homeostasis.

scholarly journals BMP signaling alters aquaporin-4 expression in the mouse cerebral cortex

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kazuya Morita ◽  
Naoyuki Matsumoto ◽  
Kengo Saito ◽  
Toshihide Hamabe-Horiike ◽  
Keishi Mizuguchi ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Molecular Mechanisms ◽  
Water Movement ◽  
Water Channel ◽  
Bmp Signaling ◽  
Aquaporin 4 ◽  
Mammalian Brain ◽  
Physiological Conditions ◽  
Pathological Conditions ◽  
Mouse Cerebral Cortex

AbstractAquaporin-4 (AQP4) is a predominant water channel expressed in astrocytes in the mammalian brain. AQP4 is crucial for the regulation of homeostatic water movement across the blood–brain barrier (BBB). Although the molecular mechanisms regulating AQP4 levels in the cerebral cortex under pathological conditions have been intensively investigated, those under normal physiological conditions are not fully understood. Here we demonstrate that AQP4 is selectively expressed in astrocytes in the mouse cerebral cortex during development. BMP signaling was preferentially activated in AQP4-positive astrocytes. Furthermore, activation of BMP signaling by in utero electroporation markedly increased AQP4 levels in the cerebral cortex, and inhibition of BMP signaling strongly suppressed them. These results indicate that BMP signaling alters AQP4 levels in the mouse cerebral cortex during development.

Water transport across mammalian cell membranes

1996 ◽  
Vol 270 (1) ◽  
pp. C12-C30 ◽  
Author(s):  
A. S. Verkman ◽  
A. N. van Hoek ◽  
T. Ma ◽  
A. Frigeri ◽  
W. R. Skach ◽  
...  
Keyword(s):  
Water Transport ◽  
Cell Membranes ◽  
Water Channel ◽  
Water Channels ◽  
Channel Structure ◽  
Level Information ◽  
Selective Channel ◽  
Transcriptional Units ◽  
Measurement Strategies

This review summarizes recent progress in water-transporting mechanisms across cell membranes. Modern biophysical concepts of water transport and new measurement strategies are evaluated. A family of water-transporting proteins (water channels, aquaporins) has been identified, consisting of small hydrophobic proteins expressed widely in epithelial and nonepithelial tissues. The functional properties, genetics, and cellular distributions of these proteins are summarized. The majority of molecular-level information about water-transporting mechanisms comes from studies on CHIP28, a 28-kDa glycoprotein that forms tetramers in membranes; each monomer contains six putative helical domains surrounding a central aqueous pathway and functions independently as a water-selective channel. Only mutations in the vasopressin-sensitive water channel have been shown to cause human disease (non-X-linked congenital nephrogenic diabetes insipidus); the physiological significance of other water channels remains unproven. One mercurial-insensitive water channel has been identified, which has the unique feature of multiple overlapping transcriptional units. Systems for expression of water channel proteins are described, including Xenopus oocytes, mammalian and insect cells, and bacteria. Further work should be directed at elucidation of the role of water channels in normal physiology and disease, molecular analysis of regulatory mechanisms, and water channel structure determination at atomic resolution.

Progesterone inhibition of water permeability in Bufo arenarum oocytes and urinary bladder

1996 ◽  
Vol 270 (5) ◽  
pp. F880-F885 ◽  
Author(s):  
P. Ford ◽  
G. Amodeo ◽  
C. Capurro ◽  
C. Ibarra ◽  
R. Dorr ◽  
...  
Keyword(s):  
Urinary Bladder ◽  
Xenopus Laevis ◽  
Water Permeability ◽  
Water Channel ◽  
Water Channels ◽  
Toad Urinary Bladder ◽  
Osmotic Permeability ◽  
Bufo Arenarum ◽  
Mrna Extraction

The ovarian oocytes from Bufo arenarum (BAO) but not those from Xenopus laevis (XLO) would have water channels (WC). We now report that the injection of the mRNA from BAO into the oocytes from XLO increased their water osmotic permeability (Pi) (reduced by 0.3 mM HgCl2 and reversed by 5 mM beta-mercaptoethanol). A 30-min challenge with progesterone induced, 18 h later, a reduction of the mercury-sensitive fraction of Pf in the BAO (but not in XLO). The mRNA from BAO pretreated with progesterone lost its capacity to induce WC in the XLO, but the hormone did not affect the expression of the WC in XLO previously injected with the mRNA from BAO. Pf was also measured in urinary bladders of BAO. Eighteen hours after a challenge with progesterone, a reduction in the hydrosmotic response to oxytocin was observed. Finally, the mRNA from the urinary bladder of BAO was injected into XLO. An increase in Pf was observed. This was not the case if, before the mRNA extraction, the bladders were treated with progesterone. We conclude that the BAO WC share progesterone sensitivity with the oxytocin-regulated water channel present in the toad urinary bladder.

Design Considerations for Artificial Water Channel–Based Membranes

2018 ◽  
Vol 48 (1) ◽  
pp. 57-82 ◽  
Author(s):  
Woochul Song ◽  
Chao Lang ◽  
Yue-xiao Shen ◽  
Manish Kumar
Keyword(s):  
Historical Perspective ◽  
Water Channel ◽  
Water Channels ◽  
Structure And Properties ◽  
High Permeability ◽  
Functional Elements ◽  
Design Considerations ◽  
Biological Water ◽  
Naturally Occurring ◽  
Artificial Water

Aquaporins (AQPs) are naturally occurring water channel proteins. They can facilitate water molecule translocation across cellular membranes with exceptional selectivity and high permeability that are unmatched in synthetic membrane systems. These unique properties of AQPs have led to their use as functional elements in membranes in recent years. However, the intricate nature of AQPs and concerns regarding their stability and processability have encouraged researchers to develop synthetic channels that mimic the structure and properties of AQPs and other biological water-conducting channels. These channels have been termed artificial water channels. This article reviews current progress and provides a historical perspective as well as an outlook toward developing scalable membranes based on artificial water channels.

Conformational dynamics and interfacial interactions of peptide-appended pillar[5]arene water channels in biomimetic membranes

2019 ◽  
Vol 21 (41) ◽  
pp. 22711-22721 ◽  
Author(s):  
Yong Liu ◽  
Harish Vashisth
Keyword(s):  
Water Purification ◽  
Conformational Dynamics ◽  
Water Channel ◽  
Water Channels ◽  
Interfacial Interactions ◽  
Biomimetic Membranes ◽  
Channel Proteins ◽  
Significant Potential ◽  
Biological Water ◽  
Artificial Water

Peptide appended pillar[5]arene (PAP) is an artificial water channel resembling biological water channel proteins, which has shown a significant potential for designing bioinspired water purification systems.

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