Molecular mechanisms of renal magnesium reabsorption

Magnesiumisan essential cofactor inmanycellularprocesses, andaberrations inmagnesiumhomeostasis can have life-threatening consequences. The kidney plays a central role inmaintaining serummagnesiumwithin a narrowrange (0.70-1.10mmol/L). Along the proximal tubule and thick ascending limb,magnesiumreabsorption occurs via paracellular pathways.Members of the claudin family formthemagnesiumpores in these segments, and also regulate magnesium reabsorption by adjusting the transepithelial voltage that drives it. Along the distal convoluted tubule transcellular reabsorption via heteromeric TRPM6/7 channels predominates, although paracellular reabsorptionmay also occur. In this segment, theNaCl cotransporter plays a critical role in determining transcellular magnesium reabsorption. Although the general machinery involved in renal magnesium reabsorption has been identified by studying genetic forms of magnesium imbalance, the mechanisms regulating it are poorly understood. This review discusses pathways of renal magnesium reabsorptionby different segments of the nephron,emphasizing newer findings thatprovide insight into regulatory process, and outlining critical unanswered questions.