Magnesium Transport in the Renal Distal Convoluted Tubule

Abstract

The distal tubule reabsorbs approximately 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 diuretics amiloride and chlorothiazide stimulate Mg(2+) 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 Mg(2+) balance. Although it is clear that many influences affect Mg(2+) transport within the DCT, the transport processes have not been identified.

Acute effect of high-calcium milk with or without additional magnesium, or calcium phosphate on parathyroid hormone and biochemical markers of bone resorption

“…Alternatively, increased Mg losses may reflect hypercalcaemiainduced changes in renal reabsorption of Mg. One might expect dietary Ca to inhibit Mg reabsorption in the nephron because of the decrease in PTH. This hormone is known to enhance Mg uptake in the distal convoluted tubule of the nephron (Dai et al, 2001). This is in agreement with our observation of a positive correlation between the 8 h postprandial urinary Mg excretion and the integrated change in serum PTH over 8 h. However, this correlation may simply reflect a short-term relationship between circulating PTH and magnesium, and therefore it may not have any longterm biological importance.…”

“…This is in agreement with our observation of a positive correlation between the 8 h postprandial urinary Mg excretion and the integrated change in serum PTH over 8 h. However, this correlation may simply reflect a short-term relationship between circulating PTH and magnesium, and therefore it may not have any longterm biological importance. Further, an increase in serum Ca or Mg each inhibit both Ca and Mg reabsorption in the kidney, which is attributed to an extracellular Ca 2þ =Mg 2þ -sensing receptor located in the cortical thick ascending limb of the loop of Henlé (Dai et al, 2001). Although the additional Mg losses following the high-Ca drinks in the present study were small, if extrapolated to a 24 h period they could amount to approximately 5 -10% of the recommended daily intake.…”

Emerging roles of TRPM6/TRPM7 channel kinase signal transduction complexes

“…At present, our mechanistic understanding of the molecular events controlling Mg 2+ homeostasis at the cellular level have eluded detailed analysis (Dai et al 2001;Konrad et al 2004;Quamme and de Rouffignac 2000). Mg 2+ plays a vital role in virtually all cellular pathways as a co-factor of many enzymes, an essential structural element of proteins and nucleic acids and a modulator of ion channels (Grubbs 2002;Konrad and Weber 2003;Konrad et al 2004;Romani and Maguire 2002;Wolf et al 2003).…”

New TRPM6 missense mutations linked to hypomagnesemia with secondary hypocalcemia

“…8 Subsequently, fine-tuning of Mg 2 þ excretion takes place in the distal convoluted tubule (DCT), where Mg 2 þ is reabsorbed via an active transcellular pathway. 9 Extensive genetic analyses of different families suffering from HSH led to the identification of the TRPM6 gene as an essential player for systemic Mg 2 þ regulation, as emphasized by the severe drop in serum Mg 2 þ levels together with renal Mg 2 þ wasting in those patients. 10,11 TRPM6 functions as a constitutively active cation channel highly permeable to Mg 2 þ .…”