Article ; Online: Molecular determinants of magnesium homeostasis: insights from human disease.
Journal of the American Society of Nephrology : JASN
2008 Volume 19, Issue 8, Page(s) 1451–1458
Abstract: The past decade has witnessed multiple advances in our understanding of magnesium (Mg(2+ ... for familial hypomagnesemia with hypercalciuria and nephrocalcinosis provided insight into the molecular ... homeostasis. The discovery that mutations in claudin-16/paracellin-1 or claudin-19 are responsible ...
| Abstract | The past decade has witnessed multiple advances in our understanding of magnesium (Mg(2+)) homeostasis. The discovery that mutations in claudin-16/paracellin-1 or claudin-19 are responsible for familial hypomagnesemia with hypercalciuria and nephrocalcinosis provided insight into the molecular mechanisms governing paracellular transport of Mg(2+). Our understanding of the transcellular movement of Mg(2+) was similarly enhanced by the realization that defects in transient receptor potential melastatin 6 (TRPM6) cause hypomagnesemia with secondary hypocalcemia. This channel regulates the apical entry of Mg(2+) into epithelia. In so doing, TRPM6 alters whole-body Mg(2+) homeostasis by controlling urinary excretion. Consequently, investigation into the regulation of TRPM6 has increased. Acid-base status, 17beta estradiol, and the immunosuppressive agents FK506 and cyclosporine affect plasma Mg(2+) levels by altering TRPM6 expression. A mutation in epithelial growth factor is responsible for isolated autosomal recessive hypomagnesemia, and epithelial growth factor activates TRPM6. A defect in the gamma-subunit of the Na,K-ATPase causes isolated dominant hypomagnesemia by altering TRPM6 activity through a decrease in the driving force for apical Mg(2+) influx. We anticipate that the next decade will provide further detail into the control of the gatekeeper TRPM6 and, therefore, overall whole-body Mg(2+) balance. |
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| MeSH term(s) | Animals ; Bone and Bones/metabolism ; Homeostasis ; Humans ; Intestinal Mucosa/metabolism ; Kidney/metabolism ; Magnesium/metabolism ; Metabolic Diseases ; TRPM Cation Channels/metabolism | |||||
| Chemical Substances | TRPM Cation Channels ; TRPM6 protein, human ; Magnesium (I38ZP9992A) | |||||
| Language | English | |||||
| Publishing date | 2008-06-18 | |||||
| Publishing country | United States | |||||
| Document type | Journal Article ; Research Support, Non-U.S. Gov't ; Review | |||||
| ZDB-ID | 1085942-1 | |||||
| ISSN | 1533-3450 ; 1046-6673 | |||||
| ISSN (online) | 1533-3450 | |||||
| ISSN | 1046-6673 | |||||
| DOI | 10.1681/ASN.2008010098 | |||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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