Article

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

Nordic Centre for Water Imbalance Related Disorders, Institute of Cellular and Molecular Medicine, The Panum Institute, University of Copenhagen, Copenhagen, Denmark.
The Journal of Physiology (Impact Factor: 4.54). 11/2010; 588(Pt 21):4089-101. DOI: 10.1113/jphysiol.2010.194738
Source: PubMed

ABSTRACT Water transport by the Na+-K+-2Cl(-) cotransporter (NKCC1) was studied in confluent cultures of pigmented epithelial (PE) cells from the ciliary body of the fetal human eye. Interdependence among water, Na+ and Cl(-) fluxes mediated by NKCC1 was inferred from changes in cell water volume, monitored by intracellular self-quenching of the fluorescent dye calcein. Isosmotic removal of external Cl(-) or Na+ caused a rapid efflux of water from the cells, which was inhibited by bumetanide (10 μm). When returned to the control solution there was a rapid water influx that required the simultaneous presence of external Na+ and Cl(-). The water influx could proceed uphill, against a transmembrane osmotic gradient, suggesting that energy contained in the ion fluxes can be transferred to the water flux. The influx of water induced by changes in external [Cl(-)] saturated in a sigmoidal fashion with a Km of 60 mm, while that induced by changes in external [Na+] followed first order kinetics with a Km of about 40 mm. These parameters are consistent with ion transport mediated by NKCC1. Our findings support a previous investigation, in which we showed water transport by NKCC1 to be a result of a balance between ionic and osmotic gradients. The coupling between salt and water transport in NKCC1 represents a novel aspect of cellular water homeostasis where cells can change their volume independently of the direction of an osmotic gradient across the membrane. This has relevance for both epithelial and symmetrical cells.

Download full-text

Full-text

Available from: Thomas Zeuthen, Aug 19, 2015
0 Followers
 · 
131 Views
  • Source
    • "There is evidence that water can be transported even against osmotic gradients (Zeuthen, 2010) by coupling its movements to the transport of a substrate that energizes its uphill transport. Likely molecules for such a mechanism are the Na + /K + /2Cl – cotransporter NKCC1 (Hamann et al., 2010) and some K + /Cl – cotransporters (Zeuthen, 2010). The activity of the basolaterally localized NKCC1 of alveolar epithelial cells could mediate the uptake of water into the epithelial cells, a hypothesis that needs to be tested. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The ability to breathe air represents a fundamental step in vertebrate evolution that was accompanied by several anatomical and physiological adaptations. The morphology of the air-blood barrier is highly conserved within air-breathing vertebrates. It is formed by three different plies, which are represented by the alveolar epithelium, the basal lamina, and the endothelial layer. Besides these conserved morphological elements, another common feature of vertebrate lungs is that they contain a certain amount of fluid that covers the alveolar epithelium. The volume and composition of the alveolar fluid is regulated by transepithelial ion transport mechanisms expressed in alveolar epithelial cells. These transport mechanisms have been reviewed extensively. Therefore, the present review focuses on the properties and functional significance of the alveolar fluid. How does the fluid enter the alveoli? What is the fate of the fluid in the alveoli? What is the function of the alveolar fluid in the lungs? The review highlights the importance of the alveolar fluid, its volume and its composition. Maintenance of the fluid volume and composition within certain limits is critical to facilitate gas exchange. We propose that the alveolar fluid is an essential element of the air-blood barrier. Therefore, it is appropriate to refer to this barrier as being formed by four plies, namely (1) the thin fluid layer covering the apical membrane of the epithelial cells, (2) the epithelial cell layer, (3) the basal membrane, and (4) the endothelial cells.
    Frontiers in Physiology 05/2012; 3:146. DOI:10.3389/fphys.2012.00146 · 3.50 Impact Factor
  • Source
    The Journal of Physiology 11/2010; 588(Pt 21):4063-4. DOI:10.1113/jphysiol.2010.199521 · 4.54 Impact Factor
  • Source
    The Journal of Physiology 02/2011; 589(Pt 4):781-2. DOI:10.1113/jphysiol.2010.203919 · 4.54 Impact Factor
Show more