title: 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.
authors.affiliation: Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: L J
authors.initials: LJ
authors.lastname: Dai
authors.forename: G
authors.initials: G
authors.lastname: Ritchie
authors.forename: D
authors.initials: D
authors.lastname: Kerstan
authors.forename: H S
authors.initials: HS
authors.lastname: Kang
authors.forename: D E
authors.initials: DE
authors.lastname: Cole
authors.forename: G A
authors.initials: GA
authors.lastname: Quamme
mesh_terms: D000136:Acid-Base Equilibrium / Q000502:physiology; D000617:Aminoglycosides / Q000633:toxicity; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity; D002945:Cisplatin / Q000633:toxicity; D004232:Diuretics / Q000494:pharmacology; D006728:Hormones / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007166:Immunosuppressive Agents / Q000633:toxicity; D017136:Ion Transport / Q000187:drug effects / Q000502:physiology; D007686:Kidney Tubules, Distal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008274:Magnesium / Q000378:metabolism*; D010710:Phosphates / Q000172:deficiency / Q000378:metabolism; D011191:Potassium Deficiency / Q000378:metabolism; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface / Q000378:metabolism; D015499:Renal Tubular Transport, Inborn Errors / Q000378:metabolism
chemical_list: D000617:Aminoglycosides; D000903:Antibiotics, Antineoplastic; D004232:Diuretics; D006728:Hormones; D007166:Immunosuppressive Agents; D010710:Phosphates; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface; D008274:Magnesium; D002945:Cisplatin