Magnesium transport in the renal distal convoluted tubule

Dai LJ, Ritchie G, Kerstan D, Kang HS, Cole DE, and Quamme GA: Magnesium transport in  the renal distal convoluted tubule. Physiological Reviews 81:51-84, 2001.

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Abstract Magnesium Transport in the Renal Distal Convoluted Tubule. Physiol Rev 81: 51–84, 2001.—The distal tubule reabsorbs ;10% of the filtered Mg21, but this is 70–80% of that delivered from the loop of Henle. Because there is little Mg21 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 Mg21 reabsorption is transcellular and active. This review discusses recent evidence for selective and sensitive control of Mg21 transport in the DCT and emphasizes the importance of this control in normal and abnormal renal Mg21 conservation. Normally, Mg21 absorption is load dependent in the distal tubule, whether delivery is altered by increasing luminal Mg21 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 Mg21 uptake was concentration and voltage dependent. Peptide hormones such asparathyroid hormone, calcitonin, glucagon, and arginine vasopressin enhance Mg21 absorption in the distal tubule and stimulate Mg21 uptake into MDCT cells. Prostaglandin E2 and isoproterenol increase Mg21 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 Mg21 transport. Aldosterone does not alter basal Mg21 uptake but potentiates hormone-stimulated Mg21 entry in MDCT cells by increasing hormone-mediated cAMP formation. 1,25-Dihydroxyvitamin D3, on the other hand, stimulates basal Mg21 uptake. Elevation of plasma Mg21 or Ca21 inhibits hormone-stimulated cAMP accumulation and Mg21 uptake in MDCT cells through activation of extracellular Ca21/Mg21-sensing mechanisms. Mg21 restriction selectively increases Mg21 uptake with no effect on Ca21 absorption. This intrinsic cellular adaptation provides the sensitive and selective control of distal Mg21 transport. The distally acting diuretics amiloride and chlorothiazide stimulate Mg21 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 Mg21 balance. Although it is clear that many influences affect Mg21 transport within the DCT, the transport processes have not been identified.

little Mg21 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 Mg21 reabsorption is transcellular and active. This review discusses recent evidence
for selective and sensitive control of Mg21 transport in the DCT and emphasizes the importance of this control in
normal and abnormal renal Mg21 conservation. Normally, Mg21 absorption is load dependent in the distal tubule,
whether delivery is altered by increasing luminal Mg21 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 Mg21 uptake was concentration and voltage dependent. Peptide hormones such as parathyroid hormone,
calcitonin, glucagon, and arginine vasopressin enhance Mg21 absorption in the distal tubule and stimulate Mg21
uptake into MDCT cells. Prostaglandin E2 and isoproterenol increase Mg21 entry into MDCT cells. The current
PHYSIOLOGICAL REVIEWS
Vol. 81, No. 1, January 2001
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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 Mg21 transport. Aldosterone
does not alter basal Mg21 uptake but potentiates hormone-stimulated Mg21 entry in MDCT cells by increasing
hormone-mediated cAMP formation. 1,25-Dihydroxyvitamin D3, on the other hand, stimulates basal Mg21 uptake.
Elevation of plasma Mg21 or Ca21 inhibits hormone-stimulated cAMP accumulation and Mg21 uptake in MDCT cells
through activation of extracellular Ca21/Mg21-sensing mechanisms. Mg21 restriction selectively increases Mg21
uptake with no effect on Ca21 absorption. This intrinsic cellular adaptation provides the sensitive and selective
control of distal Mg21 transport. The distally acting diuretics amiloride and chlorothiazide stimulate Mg21 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 Mg21 balance. Although it is clear that
many influences affect Mg21 transport within the DCT, the transport processes have not been identified.
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