Cotransport of water by the Na+-K+-2Cl−cotransporter NKCC1 in mammalian epithelial cells

Hamann, Steffen; Herrera-Pérez, José Jaime; Zeuthen, Thomas; Álvarez-Leefmans, Francisco J.

doi:10.1113/jphysiol.2010.194738

Cited by 109 publications

(95 citation statements)

References 43 publications

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“…This finding implies the existence of at least one water transport pathway in mouse β-cells in addition to AQP7. In this regard, Matsumura and colleagues [5] noted the expression of AQP8 in mouse β-cells, whilst the Na/ K/2Cl transporter NKCC1, also expressed in β-cells [20], has been reported to act as a water co-transporter [21]. The present study confirms the expression of AQP8 and reveals that of AQP5 in mouse β-cells.…”

Section: Discussionsupporting

confidence: 79%

A New Role for Aquaporin 7 in Insulin Secretion

Louchami

Best

Brown

et al. 2012

Cell Physiol Biochem

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Bacgrouns/Aims: Several insulinotropic agents were recently reported to cause β-cell swelling. The possible participation of AQP7 to water transport was investigated in AQP7^{+/ +} or AQP7^-/- mice. Methods: Aquaporin expression, insulin secretion, cell swelling and electrical activity were investigated in pancreatic islets. Results: RT-PCR revealed the expression of AQP5 and AQP8 mRNA. Double immunofluorescent labeling indicated their presence in β-cells. Whilst basal insulin release from isolated pancreatic islets incubated at 2.8 mM D-glucose did not differ between AQP7^{+/ +} or AQP7^-/- mice, the secretion of insulin evoked by the omission of 50 mM NaCl, the substitution of 50 mM NaCl by 100 mM glycerol or a rise in D-glucose concentration to 8.3 mM and 16.7 mM was severely impaired in the islets from AQP7^-/- mice. Yet, exposure of β-cells to either the hypotonic medium or a rise in D-glucose concentration caused a similar degree of swelling and comparable pattern of electrical activity in cells from AQP7^{+/ +} and AQP7^-/- mice. Both the cell swelling and change in membrane potential were only impaired in AQP7^-/- cells when exposed to 50 mM glycerol. Conclusion: It is proposed, therefore, that AQP7 may, directly or indirectly, play a role at a distal site in the exocytotic pathway.

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Section: Discussionsupporting

confidence: 79%

A New Role for Aquaporin 7 in Insulin Secretion

Louchami

Best

Brown

et al. 2012

Cell Physiol Biochem

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“…NH 4 + can potently replace K + in stimulation of the Na + ,K + -ATPase and active Na + transport [135,136] as well as the associated increase in oxygen consumption [137,138]. Expression and phosphorylation of NKCC1, a cotransporter of Na + , K + , 2 Cl − and water [139][140][141] are increased in ammonia-treated cultured astrocytes and in brain slices from thioacetamide-rats with a delay of 3-6 h (Fig. 5) [142,143].…”

Section: Effects Of Hyperammonemia Due To Similarity With Catalytic Amentioning

confidence: 99%

Multifactorial Effects on Different Types of Brain Cells Contribute to Ammonia Toxicity

et al. 2016

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Effects of ammonia on astrocytes play a major role in hepatic encephalopathy, acute liver failure and other diseases caused by increased arterial ammonia concentrations (e.g., inborn errors of metabolism, drug or mushroom poisoning). There is a direct correlation between arterial ammonia concentration, brain ammonia level and disease severity. However, the pathophysiology of hyperammonemic diseases is disputed. One long recognized factor is that increased brain ammonia triggers its own detoxification by glutamine formation from glutamate. This is an astrocytic process due to the selective expression of the glutamine synthetase in astrocytes. A possible deleterious effect of the resulting increase in glutamine concentration has repeatedly been discussed and is supported by improvement of some pathologic effects by GS inhibition. However, this procedure also inhibits a large part of astrocytic energy metabolism and may prevent astrocytes from responding to pathogenic factors. A decrease of the already low glutamate concentration in astrocytes due to increased synthesis of glutamine inhibits the malate-aspartate shuttle and energy metabolism. A more recently described pathogenic factor is the resemblance between NH and K in their effects on the Na,K-ATPase and the Na,K, 2 Cl and water transporter NKCC1. Stimulation of the Na,K-ATPase driven NKCC1 in both astrocytes and endothelial cells is essential for the development of brain edema. Na,K-ATPase stimulation also activates production of endogenous ouabains. This leads to oxidative and nitrosative damage and sensitizes NKCC1. Administration of ouabain antagonists may accordingly have therapeutic potential in hyperammonemic diseases.

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“…In addition, recent findings suggest that NKCC1 may also cotransport water along with ions (22), making it ideally suited to transport salt and water across the cell membrane required for cytoplasmic cell volume regulation.…”

Section: CLmentioning

confidence: 99%

“…7 demonstrating the dependency of NKCC1 activation on WNK3. Additionally, recent evidence showing that water moves through the pore of NKCC1 (22) uniquely positions WNK3 to aid in cell volume regulation through regulation of NKCC1 activity. In the context of gliomas and other cancers, the ability to metastasize, migrate, and invade surrounding tissue away from the original tumor site is a key phenotype.…”

Section: Disscussionmentioning

confidence: 99%

With-No-Lysine Kinase 3 (WNK3) stimulates glioma invasion by regulating cell volume

Haas

Cuddapah

Watkins

et al. 2011

American Journal of Physiology-Cell Physiology

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Among the most prevalent and deadly primary brain tumors, high-grade gliomas evade complete surgical resection by diffuse invasion into surrounding brain parenchyma. Navigating through tight extracellular spaces requires invading glioma cells to alter their shape and volume. Cell volume changes are achieved through transmembrane transport of osmolytes along with obligated water. The sodium-potassium-chloride cotransporter isoform-1 (NKCC1) plays a pivotal role in this process, and previous work has demonstrated that NKCC1 inhibition compromises glioma invasion in vitro and in vivo by interfering with the required cell volume changes. In this study, we show that NKCC1 activity in gliomas requires the With-No-Lysine Kinase-3 (WNK3) kinase. Western blots of patient biopsies and patientderived cell lines shows prominent expression of Ste-20-related, prolinealanine-rich kinase (SPAK), oxidative stress response kinase (OSR1), and WNK family members 1, 3, and 4. Of these, only WNK3 colocalized and coimmunoprecipitated with NKCC1 upon changes in cell volume. Stable knockdown of WNK3 using specific short hairpin RNA constructs completely abolished NKCC1 activity, as measured by the loss of bumetanide-sensitive cell volume regulation. Consequently, WNK3 knockdown cells showed a reduced ability to invade across Transwell barriers and lacked bumetanide-sensitive migration. This data indicates that WNK3 is an essential regulator of NKCC1 and that WNK3 activates NKCC1-mediated ion transport necessary for cell volume changes associated with cell invasion. cell migration; chloride transport; neurobiology; neurological diseases; sodium-potassium-chloride cotransporter isoform-1 GLIOMAS, brain tumors thought to originate from glial cells, are among the most problematic primary cancers to treat. This is in part due to their propensity to penetrate surrounding brain tissue (23), thereby evading complete surgical resection. Unique to gliomas, tumor spread does not occur hematogenously, but rather, glioma cells invade and migrate into neighboring brain parenchyma guided by white matter tracts and blood vessels (15). Ion channel activity aids the rapid and dynamic volume and shape changes required to alter cellular volume (45). To modify cell volume, gliomas capitalize on ion release, most notably K ϩ and Cl Ϫ , to couple osmotically obligated water movement (43, 44). Ions must be concentrated intracellularly to favor their efflux down electrochemical gradients to provide this function, and previous research has demonstrated that sodium-potassium-chloride cotransporter isoform-1 (NKCC1) is likely responsible for ClϪ accumulation in the cell, playing an integral role in hyperosmotic volume regulation and cell migration and invasion both in vitro and in vivo (9, 18). In addition, recent findings suggest that NKCC1 may also cotransport water along with ions (22), making it ideally suited to transport salt and water across the cell membrane required for cytoplasmic cell volume regulation.To be exploited by gliomas to aid in migration and ...

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Cotransport of water by the Na⁺-K⁺-2Cl⁻cotransporter NKCC1 in mammalian epithelial cells

Cited by 109 publications

References 43 publications

A New Role for Aquaporin 7 in Insulin Secretion

A New Role for Aquaporin 7 in Insulin Secretion

Multifactorial Effects on Different Types of Brain Cells Contribute to Ammonia Toxicity

With-No-Lysine Kinase 3 (WNK3) stimulates glioma invasion by regulating cell volume

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