TRPM6 forms the Mg2+ influx channel involved in intestinal and renal Mg2+ absorption.

摘要: Mg2+ is an essential ion involved in a multitude of physiological and biochemical processes major constituent bone tissue. homeostasis mammals depends on the equilibrium between intestinal absorption renal excretion, but little known about molecular nature proteins transepithelial transport these organs. Recently, it was shown that patients with mutations TRPM6, member transient receptor potential family cation channels, suffer from hypomagnesemia secondary hypocalcemia (HSH) as result impaired and/or handling. Here, we show TRPM6 specifically localized along apical membrane distal convoluted tubule brush-border small intestine, epithelia particularly associated active (re)absorption. In kidney, parvalbumin calbindin-D28K, two divalent-binding proteins, are co-expressed might function intracellular buffers tubule. Heterologous expression wild-type not mutants identified HSH induces Mg2+- Ca2+-permeable channel tightly regulated by levels. The TRPM6-induced displays strong outward rectification, has 5-fold higher affinity for than Ca2+, blocked voltage-dependent manner ruthenium red. Our data indicate comprises all or part Mg2+-absorbing epithelia.