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Essential role for TRPM6 in epithelial magnesium transport and body magnesium homeostasis

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Abstract

Magnesium is an important cofactor for many biological processes such as protein synthesis, nucleic acid stability and neuromuscular excitability. The extracellular magnesium concentration is regulated tightly by the extent of intestinal absorption and renal excretion. Despite their critical role in magnesium handling, the molecular mechanisms mediating transepithelial transport are still not understood completely. Recently, genetic studies in patients with primary hypomagnesaemia and secondary hypocalcaemia (HSH), a combined defect of intestinal magnesium absorption and renal magnesium conservation, have identified “transient receptor potential (melastatin) 6” (TRPM6) as the first component involved directly in epithelial magnesium reabsorption. TRPM7, the closest homologue of TRPM6, has a central role in Mg2+ uptake in vertebrate cells since TRPM7-deficient cells become Mg2+ deficient and are not viable. TRPM7 has been characterized functionally as a constitutively active ion channel permeable for a variety of cations including calcium and magnesium and regulated by intracellular concentrations of magnesium and/or magnesium-nucleotide complexes. Both proteins share the unique feature of cation channels fused to serine/threonine kinase domains. This review summarizes recent data that has emerged from molecular genetic, biochemical and electrophysiological studies on these fascinating two new proteins and their involvement in epithelial magnesium transport.

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Authors and Affiliations

  1. Institute of Pharmacology and Toxicology, Philipps-University, Marburg, Germany

    Vladimir Chubanov & Thomas Gudermann

  2. University Children’s Hospital, Philipps-University, Deutschhausstrasse 12, 35037, Marburg, Germany

    Karl P. Schlingmann

Authors
  1. Vladimir Chubanov
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  2. Thomas Gudermann
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  3. Karl P. Schlingmann
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Correspondence to Karl P. Schlingmann.

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Chubanov, V., Gudermann, T. & Schlingmann, K.P. Essential role for TRPM6 in epithelial magnesium transport and body magnesium homeostasis. Pflugers Arch - Eur J Physiol 451, 228–234 (2005). https://doi.org/10.1007/s00424-005-1470-y

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