Magnesium Transport in the Renal Distal Convoluted Tubule

Department of Medicine, University of British Columbia, Vancouver, British Columbia; and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada Dai, Long-Jun, Gordon Ritchie, Dirk Kerstan, Hyung Sub Kang, David E. C. Cole, and Gary A. Quamme. Magnesium Transport in the Renal Distal Convoluted Tubule. Physiol. Rev. 81: 51-84, 2001. The distal tubule reabsorbs ~10% of the filtered Mg 2+ , but this is 70-80% of that delivered from the loop of Henle. Because there is little Mg 2+ reabsorption beyond the distal tubule, this segment plays an important role in determining the final urinary excretion. The distal convoluted segment (DCT) is characterized by a negative luminal voltage and high intercellular resistance so that Mg 2+ reabsorption is transcellular and active. This review discusses recent evidence for selective and sensitive control of Mg 2+ transport in the DCT and emphasizes the importance of this control in normal and abnormal renal Mg 2+ conservation. Normally, Mg 2+ absorption is load dependent in the distal tubule, whether delivery is altered by increasing luminal Mg 2+ concentration or increasing the flow rate into the DCT. With the use of microfluorescent studies with an established mouse distal convoluted tubule (MDCT) cell line, it was shown that Mg 2+ uptake was concentration and voltage dependent. Peptide hormones such as parathyroid hormone, calcitonin, glucagon, and arginine vasopressin enhance Mg 2+ absorption in the distal tubule and stimulate Mg 2+ uptake into MDCT cells. Prostaglandin E 2 and isoproterenol increase Mg 2+ entry into MDCT cells. The current evidence indicates that cAMP-dependent protein kinase A, phospholipase C, and protein kinase C signaling pathways are involved in these responses. Steroid hormones have significant effects on distal Mg 2+ transport. Aldosterone does not alter basal Mg 2+ uptake but potentiates hormone-stimulated Mg 2+ entry in MDCT cells by increasing hormone-mediated cAMP formation. 1,25-Dihydroxyvitamin D 3 , on the other hand, stimulates basal Mg 2+ uptake. Elevation of plasma Mg 2+ or Ca 2+ inhibits hormone-stimulated cAMP accumulation and Mg 2+ uptake in MDCT cells through activation of extracellular Ca 2+ /Mg 2+ -sensing mechanisms. Mg 2+ restriction selectively increases Mg 2+ uptake with no effect on Ca 2+ absorption. This intrinsic cellular adaptation provides the sensitive and selective control of distal Mg 2+ transport. The distally acting diuret