Renal Mg handling, FXYD2 and the central role of the Na, K‐ATPase. Issue 17 (2nd September 2018)

• Record Type: Journal Article
• Authors: Mayan, Haim; Farfel, Zvi; Karlish, Steven J. D.
• Is Part Of: Physiological reports. Volume 6:Issue 17(2018)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2018-09-02
• Subjects: FXYD2 -- Na -- K‐ATPase -- renal Mg handling -- tubulopathies; Physiology -- Periodicals; 571
• DOI: 10.14814/phy2.13843
• Languages: English
• ISSNs: 2051-817X

Abstract

Abstract: This article examines the central role of Na, K‐ATPase ( α 1 β 1FXYD2) 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 K0.5 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. Abstract : Renal Mg balance is regulated mainly in the distal convoluted tubule (DCT). This article discusses detailed molecular and cellular mechanisms by which Na, K‐ATPase activity in DCT determines Mg transport in normal kidneys and in disease states that affect Mg balance (FXYD2 and HNF‐B1 mutations, Gitelmans syndrome, Familial Hyperkalemia and Hypertension (FHHt)).