The epithelial Mg2+ channel transient receptor potential melastatin 6 is regulated by dietary Mg2+ content and estrogens

Journal of the American Society of Nephrology : JASN
Wouter M Tiel GroenestegeRené J M Bindels

Abstract

The kidney is the principal organ responsible for the regulation of the body Mg(2+) balance. Identification of the gene defect in hypomagnesemia with secondary hypocalcemia recently elucidated transient receptor potential melastatin 6 (TRPM6) as the gatekeeper in transepithelial Mg(2+) transport, whereas its homolog, TRPM7, is implicated in cellular Mg(2+) homeostasis. The aim of this study was to determine the tissue distribution in mouse and regulation of TRPM6 and TRPM7 by dietary Mg(2+) and hormones. This study demonstrates that TRPM6 is expressed predominantly in kidney, lung, cecum, and colon, whereas TRPM7 is distributed ubiquitously. Dietary Mg(2+) restriction in mice resulted in hypomagnesemia and renal Mg(2+) and Ca(2+) conservation, whereas a Mg(2+)-enriched diet led to increased urinary Mg(2+) and Ca(2+) excretion. Conversely, Mg(2+) restriction significantly upregulated renal TRPM6 mRNA levels, whereas a Mg(2+) enriched diet increased TRPM6 mRNA expression in colon. Dietary Mg(2+) did not alter TRPM7 mRNA expression in mouse kidney and colon. In addition, it was demonstrated that 17beta-estradiol but not 1,25-dihydroxyvitamin D(3) or parathyroid hormone regulates TRPM6 renal mRNA levels. Renal TRPM7 mRNA abundance ...Continue Reading

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