Regulation of renal Na+,K(+)‐ATPase in rat thick ascending limb during K+ depletion: evidence for modulation of Na+ affinity.

Buffin-Meyer, Bénédicte; Marsy, S.; Barlet-Bas, C.; Cheval, Lydie; Younes-Ibrahim, Maurício; Rajerison, Rabary; Doucet, Alain

doi:10.1113/jphysiol.1996.sp021172

Cited by 19 publications

(10 citation statements)

References 29 publications

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“…The injection of CHIF cRNA into Xenopus oocytes, in contrast, resulted in an increase in apparent affinity for Na ϩ (32). Taken together with the almost complementary distributions of ␥ and CHIF along the rat nephron (16,22), the functional data correlate very well with the differences in Na ϩ affinities in successive segments of the nephron (4,6,7,33).…”

supporting

confidence: 62%

Differential Regulation of Renal Na,K-ATPase by Splice Variants of the γ Subunit

Arystarkhova

Donnet

Asinovski

et al. 2002

Journal of Biological Chemistry

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Sodium and potassium-exchanging adenosine triphosphatase (Na,K-ATPase) in the kidney is associated with the ␥ subunit (␥, FXYD2), a single-span membrane protein that modulates ATPase properties. Rat and human ␥ occur in two splice variants, ␥a and ␥b, with different N termini. Here we investigated their structural heterogeneity and functional effects on Na,K-ATPase properties. Both forms were post-translationally modified during in vitro translation with microsomes, indicating that there are four possible forms of ␥. Site-directed mutagenesis revealed Thr 2 and Ser 5 as potential sites for post-translational modification. Similar modification can occur in cells, with consequences for Na,K-ATPase properties. We showed previously that stable transfection of ␥a into NRK-52E cells resulted in reduction of apparent affinities for Na ؉ and K ؉ . Individual clones differed in ␥ post-translational modification, however, and the effect on Na ؉ affinity was absent in clones with full modification. Here, transfection of ␥b also resulted in clones with or without post-translational modification. Both groups showed a reduction in Na ؉ affinity, but modification was required for the effect on K ؉ affinity. There were minor increases in ATP affinity. The physiological importance of the reduction in Na ؉ affinity was shown by the slower growth of ␥a, ␥b, and ␥b transfectants in culture. The differential influence of the four structural variants of ␥ on affinities of the Na,KATPase for Na ؉ and K ؉ , together with our previous finding of different distributions of ␥a and ␥b along the rat nephron, suggests a highly specific mode of regulation of sodium pump properties in kidney.

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supporting

confidence: 62%

Differential Regulation of Renal Na,K-ATPase by Splice Variants of the γ Subunit

Arystarkhova

Donnet

Asinovski

et al. 2002

Journal of Biological Chemistry

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“…K ϩ depletion has been used extensively to inhibit Na,K-ATPase activity in various cell types (9,45,46) and, in particular, in RPE cells (21,41,42). In this method, the pump can be reactivated by repleting K ϩ , and therefore the reversibility of the effects of Na,K-ATPase inhibition can be studied (48).…”

Section: Resultsmentioning

confidence: 99%

Na,K-ATPase inhibition alters tight junction structure and permeability in human retinal pigment epithelial cells

Rajasekaran¹,

Hu²,

Gopal³

et al. 2003

American Journal of Physiology-Cell Physiology

106

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Na,K-ATPase regulates a variety of transport functions in epithelial cells. In cultures of human retinal pigment epithelial (RPE) cells, inhibition of Na,K-ATPase by ouabain and K+ depletion decreased transepithelial electrical resistance (TER) and increased permeability of tight junctions to mannitol and inulin. Electrophysiological studies demonstrated that the decrease in TER was due to an increase in paracellular shunt conductance. At the light microscopy level, this increased permeability was not accompanied by changes in the localization of the tight junction proteins ZO-1, occludin, and claudin-3. At the ultrastructural level, increased tight junction permeability correlated with a decrease in tight junction membrane contact points. Decreased tight junction membrane contact points and increased tight junction permeability were reversible in K+-repletion experiments. Confocal microscopy revealed that in control cells, Na,K-ATPase was localized at both apical and basolateral plasma membranes. K+ depletion resulted in a large reduction of apical Na,K-ATPase, and after K+repletion the apical Na,K-ATPase recovered to control levels. These results suggest a functional link exists between Na,K-ATPase and tight junction function in human RPE cells.

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“…Pathways that alter ion affinities of kidney Na,K-ATPase consequent to hormone treatment or electrolyte dietary restriction have been reported (4,5,28,29). Their molecular mechanisms are still obscure, however, and could entail the expression and/or modification of ␥.…”

Section: Discussionmentioning

confidence: 99%

“…Small changes in Na,K-ATPase ion affinities can have important physiological effects both directly on transepithelial ion and fluid transport and indirectly through the ion gradients used by other transporters (1,2). In permeabilized microdissected nephron segments, Na,K-ATPase has increased affinity for Na ϩ in thick ascending limb compared with proximal convoluted tubule and has still higher affinity in cortical collecting tubule (3)(4)(5)(6). Although isoforms of ␣ and ␤ can have different ion affinities (7), isoforms unique to the nephron segments with higher affinity have not been detected (8 -12), leaving the mechanism unexplained.…”

mentioning

confidence: 99%

The γ Subunit Modulates Na+ and K+Affinity of the Renal Na,K-ATPase

Arystarkhova

Wetzel

Asinovski

et al. 1999

Journal of Biological Chemistry

185

186

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The Na؉ ,K ؉ -ATPase catalyzes the active transport of ions. It has two necessary subunits, ␣ and ␤, but in kidney it is also associated with a 7.4-kDa protein, the ␥ subunit. Stable transfection was used to determine the effect of ␥ on Na,K-ATPase properties. When isolated from either kidney or transfected cells, ␣␤␥ had lower affinities for both Na ؉ and K ؉ than ␣␤. A post-translational modification of ␥ selectively eliminated the effect on Na ؉ affinity, suggesting three configurations (␣␤, ␣␤␥, and ␣␤␥*) conferring different stable properties to Na,K-ATPase. In the nephron, segment-specific differences in Na ؉ affinity have been reported that cannot be explained by the known ␣ and ␤ subunit isoforms of Na,K-ATPase. Immunofluorescence was used to detect ␥ in rat renal cortex. Cortical ascending limb and some cortical collecting tubules lacked ␥, correlating with higher Na ؉ affinities in those segments reported in the literature. Selective expression in different segments of the nephron is consistent with a modulatory role for the ␥ subunit in renal physiology.

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Regulation of renal Na+,K(+)‐ATPase in rat thick ascending limb during K+ depletion: evidence for modulation of Na+ affinity.

Cited by 19 publications

References 29 publications

Differential Regulation of Renal Na,K-ATPase by Splice Variants of the γ Subunit

Differential Regulation of Renal Na,K-ATPase by Splice Variants of the γ Subunit

Na,K-ATPase inhibition alters tight junction structure and permeability in human retinal pigment epithelial cells

The γ Subunit Modulates Na+ and K+Affinity of the Renal Na,K-ATPase

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