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WATER AND ELECTROLYTE HOMEOSTASIS

Relationship between low magnesium status and TRPM6 expression in the kidney and large intestine

¹Institut National de la Recherche Agronomique, Unité de Nutrition Humaine, Centre de Recherche en Nutrition Humaine d'Auvergne, Theix, St Genès Champanelle, France; and ²Department of Physiology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

Submitted 2 March 2007 ; accepted in final form 26 March 2008

The body maintains Mg²⁺ homeostasis by renal and intestinal (re)absorption. However, the molecular mechanisms that mediate transepithelial Mg²⁺ transport are largely unknown. Transient receptor potential melastatin 6 (TRPM6) was recently identified and shown to function in active epithelial Mg²⁺ transport in intestine and kidney. To define the relationship between Mg²⁺ status and TRPM6 expression, we used two models of hypomagnesemia: 1) C57BL/6J mice fed a mildly or severely Mg²⁺-deficient diet, and 2) mice selected for either low (MgL) or high (MgH) erythrocyte and plasma Mg²⁺ status. In addition, the mice were subjected to a severely Mg²⁺-deficient diet. Our results show that C57BL/6J mice fed a severely Mg²⁺-deficient diet developed hypomagnesemia and hypomagnesuria and showed increased TRPM6 expression in kidney and intestine. When fed a Mg²⁺-adequate diet, MgL mice presented hypomagnesemia and hypermagnesuria, and lower kidney and intestinal TRPM6 expression, compared with MgH mice. A severely Mg²⁺-deficient diet led to hypomagnesemia and hypomagnesuria in both strains. Furthermore, this diet induced kidney TRPM6 expression in MgL mice, but not in MgH mice. In conclusion, as shown in C57BL/6J mice, dietary Mg²⁺-restriction results in increased Mg²⁺ (re)absorption, which is correlated with increased TRPM6 expression. In MgL and MgH mice, the inherited Mg²⁺ status is linked to different TRPM6 expression. The MgL and MgH mice respond differently to a low-Mg²⁺ diet with regard to TRPM6 expression in the kidney, consistent with genetic factors contributing to the regulation of cellular Mg²⁺ levels. Further studies of these mice strains could improve our understanding of the genetics of Mg²⁺ homeostasis.

low Mg²⁺ diet; low Mg²⁺ inbred mice; active Mg²⁺ (re)absorption

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