Magnesium transport in the renal distal convoluted tubule

The distal tubule reabsorbs similar to 10% of the filtered Mg2+, but this i s 70-80% of that delivered from the loop of Henle. Because there is little Mg2+ reabsorption beyond the distal tubule, this segment plays an important role in determining the final urinary excretion. The distal convoluted seg ment (DCT) is characterized by a negative luminal voltage and high intercel lular resistance so that Mg2+ reabsorption is transcellular and active. Thi s review discusses recent evidence for selective and sensitive control of M g2+ transport in the DCT and emphasizes the importance of this control in n ormal and abnormal renal Mg2+ conservation. Normally, Mg2+ absorption is lo ad dependent in the distal tubule, whether delivery is altered by increasin g luminal Mg2+ concentration or increasing the how rate into the DCT. With the use of microfluorescent studies with an established mouse distal convol uted tubule (MDCT) cell line, it was shown that Mg2+ uptake was concentrati on and voltage dependent. Peptide hormones such as parathyroid hormone, cal citonin, glucagon, and arginine vasopressin enhance Mg2+ absorption in the distal tubule and stimulate Mg2+ uptake into MDCT cells. Prostaglandin E-2 and isoproterenol increase Mg2+ entry into MDCT cells. The current evidence indicates that cAMP-dependent protein kinase A, phospholipase C, and prote in kinase C signaling pathways are involved in these responses. Steroid hor mones have significant effects on distal Mg2+ transport. Aldosterone does n ot alter basal Mg2+ uptake but potentiates hormone-stimulated Mg2+ entry in MDCT cells by increasing hormone-mediated cAMP formation. 1,25-Dihydroxyvi tamin D-3, on the other hand, stimulates basal Mg2+ uptake. Elevation of pl asma Mg2+ or Ca2+ inhibits hormone-stimulated cAMP accumulation and Mg2+ up take in MDCT cells through activation of extracellular Ca2+/Mg2+-sensing me chanisms. Mg2+ restriction selectively increases Mg2+ uptake with no effect on Ca2+ absorption. This intrinsic cellular adaptation provides the sensit ive and selective control of distal Mg2+ transport. The distally acting diu retics amiloride and chlorothiazide stimulate Mg2+ uptake in MDCT cells act ing through changes in membrane voltage. A number of familial and acquired disorders have been described that emphasize the diversity of cellular cont rols affecting renal Mg2+ balance. Although it is clear that many influence s affect Mg2+ transport within the DCT, the transport processes have not be en identified.