%0 Journal Article
%T Renal sodium and magnesium reabsorption are not coupled in a mouse model of Gordon syndrome
%A Jenny van der Wijst
%A Paul A. Welling
%A Paul R. Grimm
%A Wouter H. van Megen
%J Archive of "Physiological Reports".
%D 2018
%R 10.14814/phy2.13728
%X Active reabsorption of magnesium (Mg2+) in the distal convoluted tubule (DCT) of the kidney is crucial for maintaining Mg2+ homeostasis. Impaired activity of the Na+©\Cl£¿©\cotransporter (NCC) has been associated with hypermagnesiuria and hypomagnesemia, while increased activity of NCC, as observed in patients with Gordon syndrome, is not associated with alterations in Mg2+ balance. To further elucidate the possible interrelationship between NCC activity and renal Mg2+ handling, plasma Mg2+ levels and urinary excretion of sodium (Na+) and Mg2+ were measured in a mouse model of Gordon syndrome. In this model, DCT1©\specific expression of a constitutively active mutant form of the NCC©\phosphorylating kinase, SPAK (CA©\SPAK), increases NCC activity and hydrochlorothiazide (HCTZ)©\sensitive Na+ reabsorption. These mice were normomagnesemic and HCTZ administration comparably reduced plasma Mg2+ levels in CA©\SPAK mice and control littermates. As inferred by the initial response to HCTZ, CA©\SPAK mice exhibited greater NCC©\dependent Na+ reabsorption together with decreased Mg2+ reabsorption, compared to controls. Following prolonged HCTZ administration (4 days), CA©\SPAK mice exhibited higher urinary Mg2+ excretion, while urinary Na+ excretion decreased to levels observed in control animals. Surprisingly, CA©\SPAK mice had unaltered renal expression of Trpm6, encoding the Mg2+©\permeable channel TRPM6, or other magnesiotropic genes. In conclusion, CA©\SPAK mice exhibit normomagnesemia, despite increased NCC activity and Na+ reabsorption. Thus, Mg2+ reabsorption is not coupled to increased thiazide©\sensitive Na+ reabsorption, suggesting a similar process explains normomagnesemia in Gordon syndrome. Further research is required to unravel the molecular underpinnings of this phenomenon and the more pronounced Mg2+ excretion after prolonged HCTZ administration
%K Gordon syndrome
%K kidney
%K magnesium
%K sodium
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6054696/