Magnesium Transport in the Renal Distal Convoluted Tubule

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Abstract
The distal tubule reabsorbs ∼10% of the filtered Mg2+, but this is 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 segment (DCT) is characterized by a negative luminal voltage and high intercellular resistance so that Mg2+ reabsorption is transcellular and active. This review discusses recent evidence for selective and sensitive control of Mg2+ transport in the DCT and emphasizes the importance of this control in normal and abnormal renal Mg2+ conservation. Normally, Mg2+ absorption is load dependent in the distal tubule, whether delivery is altered by increasing luminal Mg2+ 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 Mg2+ uptake was concentration and voltage dependent. Peptide hormones such as parathyroid hormone, calcitonin, glucagon, and arginine vasopressin enhance Mg2+ absorption in the distal tubule and stimulate Mg2+ uptake into MDCT cells. Prostaglandin E2 and isoproterenol increase Mg2+ 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 Mg2+ transport. Aldosterone does not alter basal Mg2+ uptake but potentiates hormone-stimulated Mg2+ entry in MDCT cells by increasing hormone-mediated cAMP formation. 1,25-Dihydroxyvitamin D3, on the other hand, stimulates basal Mg2+ uptake. Elevation of plasma Mg2+ or Ca2+ inhibits hormone-stimulated cAMP accumulation and Mg2+ uptake in MDCT cells through activation of extracellular Ca2+/Mg2+-sensing mechanisms. Mg2+ restriction selectively increases Mg2+uptake with no effect on Ca2+ absorption. This intrinsic cellular adaptation provides the sensitive and selective control of distal Mg2+ transport. The distally acting diuretics amiloride and chlorothiazide stimulate Mg2+ uptake in MDCT cells acting through changes in membrane voltage. A number of familial and acquired disorders have been described that emphasize the diversity of cellular controls affecting renal Mg2+ balance. Although it is clear that many influences affect Mg2+ transport within the DCT, the transport processes have not been identified.