TRPM6 Forms the Mg2+ Influx Channel Involved in Intestinal and Renal Mg2+ Absorption*
By T. Voets, B. Nilius, S. Hoefs, A. W. van der Kemp, G. Droogmans, R. Bindels, J. Hoenderop. Journal of Biological Chemistry, 2004
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Mg2+ is an essential ion involved in a multitude of physiological and biochemical processes and a major constituent of bone tissue. Mg2+ homeostasis in mammals depends on the equilibrium between intestinal Mg2+ absorption and renal Mg2+ excretion, but little is known about the molecular nature of the proteins involved in the transepithelial transport of Mg2+ in these organs. Recently, it was shown that patients with mutations in TRPM6, a member of the transient receptor potential family of cation channels, suffer from hypomagnesemia with secondary hypocalcemia (HSH) as a result of impaired renal and/or intestinal Mg2+ handling. Here, we show that TRPM6 is specifically localized along the apical membrane of the renal distal convoluted tubule and the brush-border membrane of the small intestine, epithelia particularly associated with active Mg2+ (re)absorption. In kidney, parvalbumin and calbindin-D28K, two divalent-binding proteins, are co-expressed with TRPM6 and might function as intracellular Mg2+ buffers in the distal convoluted tubule. Heterologous expression of wild-type TRPM6 but not TRPM6 mutants identified in HSH patients induces a Mg2+- and Ca2+-permeable cation channel tightly regulated by intracellular Mg2+ levels. The TRPM6-induced channel displays strong outward rectification, has a 5-fold higher affinity for Mg2+ than for Ca2+, and is blocked in a voltage-dependent manner by ruthenium red. Our data indicate that TRPM6 comprises all or part of the apical Mg2+ channel of Mg2+-absorbing epithelia.
Subfields: Nutrition and Dietetics
View Paper: https://www.semanticscholar.org/paper/2590b9325163f04c156d3da6b2a95d56f470619a
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In Nutrition and Dietetics
Citations in the corpus
- Piezos are pore-forming subunits of mechanically activated channels (2012, background): “Ruthenium red, a polycationic pore blocker of TRP channel”
- The transient receptor potential family of ion channels (2011, background): “Magnesium overload is also prevented by TRPM6, which is tightly regulated by the intracellular Mg2+ concentration [51].”
- An introduction to TRP channels. (2006, background): “0 mM), so their currents are revealed by dialyzing out or chelating [Mg2+]i (26, 147, 149).”
- The TRP Superfamily of Cation Channels (2005, background): “As with TRPM7, the TRPM6-dependent current is carried mostly by divalent cations, such as Mg2+ and Ca2+, and is inhibited by Mg2+ (166).”