Role of the distal convoluted tubule in renal Mg2+ handling: molecular lessons from inherited hypomagnesemia

In healthy individuals, Mg2+ homeostasis is tightly regulated by the concerted action of intestinal absorption, exchange with bone, and renal excretion. The kidney, more precisely the distal convoluted tubule (DCT), is the final determinant of plasma Mg2+ concentrations. Positional cloning strategies in families with hereditary hypomagnesemia identified defects in several proteins localized in the DCT as causative factors. So far, the identified actors involved in Mg2+ handling in the DCT include: the transient receptor potential channel melastatin member 6, the pro-epidermal growth factor, the thiazide-sensitive Na+-Cl- cotransporter, the gamma-subunit of the Na+/K+-ATPase, the hepatocyte nuclear factor 1B, the potassium channels Kv1.1 and Kir4.1, and the cyclin M2. In the years to come, the identification of new magnesiotropic genes and related proteins will further clarify the role of the kidney in Mg2+ homeostasis, and will potentially lead to new therapeutic approaches for hypomagnesemia.