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Renal Mg handling, FXYD2 and the central role of the Na,K‐ATPase

This article examines the central role of Na,K‐ATPase (α1β1FXYD2) in renal Mg handling, especially in distal convoluted tubule (DCT), the segment responsible for final regulation of Mg balance. By considering effects of Na,K‐ATPase on intracellular Na and K concentrations, and driving forces for Mg...

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Detalles Bibliográficos
Autores principales: Mayan, Haim, Farfel, Zvi, Karlish, Steven J. D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6119663/
https://www.ncbi.nlm.nih.gov/pubmed/30175537
http://dx.doi.org/10.14814/phy2.13843
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author Mayan, Haim
Farfel, Zvi
Karlish, Steven J. D.
author_facet Mayan, Haim
Farfel, Zvi
Karlish, Steven J. D.
author_sort Mayan, Haim
collection PubMed
description This article examines the central role of Na,K‐ATPase (α1β1FXYD2) in renal Mg handling, especially in distal convoluted tubule (DCT), the segment responsible for final regulation of Mg balance. By considering effects of Na,K‐ATPase on intracellular Na and K concentrations, and driving forces for Mg transport, we propose a consistent rationale explaining basal Mg reabsorption in DCT and altered Mg reabsorption in some human diseases. FXYD2 (γ subunit) is a regulatory subunit that adapts functional properties of Na,K‐ATPase to cellular requirements. Mutations in FXYD2 (G41R), and transcription factors (HNF‐1B and PCBD1) that affect FXYD2 expression are associated with hypomagnesemia with hypermagnesuria. These mutations result in impaired interactions of FXYD2 with Na,K‐ATPase. Renal Mg wasting implies that Na,K‐ATPase is inhibited, but in vitro studies show that FXYD2 itself inhibits Na,K‐ATPase activity, raising K(0.5)Na. However, FXYD2 also stabilizes the protein by amplifying specific interactions with phosphatidylserine and cholesterol within the membrane. Renal Mg wasting associated with impaired Na,K‐ATPase/FXYD2 interactions is explained simply by destabilization and inactivation of Na,K‐ATPase. We consider also the role of the Na,K‐ATPase in Mg (and Ca) handling in Gitelman syndrome and Familial hyperkalemia and hypertension (FHHt). Renal Mg handling serves as a convenient marker for Na,K‐ATPase activity in DCT.
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spelling pubmed-61196632018-09-05 Renal Mg handling, FXYD2 and the central role of the Na,K‐ATPase Mayan, Haim Farfel, Zvi Karlish, Steven J. D. Physiol Rep Invited Reviews This article examines the central role of Na,K‐ATPase (α1β1FXYD2) in renal Mg handling, especially in distal convoluted tubule (DCT), the segment responsible for final regulation of Mg balance. By considering effects of Na,K‐ATPase on intracellular Na and K concentrations, and driving forces for Mg transport, we propose a consistent rationale explaining basal Mg reabsorption in DCT and altered Mg reabsorption in some human diseases. FXYD2 (γ subunit) is a regulatory subunit that adapts functional properties of Na,K‐ATPase to cellular requirements. Mutations in FXYD2 (G41R), and transcription factors (HNF‐1B and PCBD1) that affect FXYD2 expression are associated with hypomagnesemia with hypermagnesuria. These mutations result in impaired interactions of FXYD2 with Na,K‐ATPase. Renal Mg wasting implies that Na,K‐ATPase is inhibited, but in vitro studies show that FXYD2 itself inhibits Na,K‐ATPase activity, raising K(0.5)Na. However, FXYD2 also stabilizes the protein by amplifying specific interactions with phosphatidylserine and cholesterol within the membrane. Renal Mg wasting associated with impaired Na,K‐ATPase/FXYD2 interactions is explained simply by destabilization and inactivation of Na,K‐ATPase. We consider also the role of the Na,K‐ATPase in Mg (and Ca) handling in Gitelman syndrome and Familial hyperkalemia and hypertension (FHHt). Renal Mg handling serves as a convenient marker for Na,K‐ATPase activity in DCT. John Wiley and Sons Inc. 2018-09-02 /pmc/articles/PMC6119663/ /pubmed/30175537 http://dx.doi.org/10.14814/phy2.13843 Text en © 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Invited Reviews
Mayan, Haim
Farfel, Zvi
Karlish, Steven J. D.
Renal Mg handling, FXYD2 and the central role of the Na,K‐ATPase
title Renal Mg handling, FXYD2 and the central role of the Na,K‐ATPase
title_full Renal Mg handling, FXYD2 and the central role of the Na,K‐ATPase
title_fullStr Renal Mg handling, FXYD2 and the central role of the Na,K‐ATPase
title_full_unstemmed Renal Mg handling, FXYD2 and the central role of the Na,K‐ATPase
title_short Renal Mg handling, FXYD2 and the central role of the Na,K‐ATPase
title_sort renal mg handling, fxyd2 and the central role of the na,k‐atpase
topic Invited Reviews
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6119663/
https://www.ncbi.nlm.nih.gov/pubmed/30175537
http://dx.doi.org/10.14814/phy2.13843
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