Dietary Mg2+ regulates the epithelial Mg2+ channel TRPM6 in rat mammary tissue.

The epithelial Mg2+ channel TRPM6 is considered a pivotal component in active Mg2+ absorption and re-absorption in the intestine and kidney, but its expression and function in other tissues are largely unknown. We have previously demonstrated that extracellular Mg2+ availability modulates TRPM6, but not the ubiquitous TRPM7, in cultured mammary epithelial cells; in addition, TRPM6 protein expression correlated to Mg2+ influx capacities. Our results closely remind the modulation of TRPM6 described by others in murine kidney and colon following Mg2+ dietary restriction. We sought to validate our observations by investigating whether TRPM6 modulation by extracellular Mg2+ also occurs in vivo. To this aim, we exploited a model consisting of rats fed either with a Mg2+-deficient or a Mg2+-enriched diet, and studied TRPM6 expression in breast and kidney tissues. Immunohistochemical and western blot analyses confirmed that rat mammary tissues express TRPM6 protein levels similar to those found in the kidney, and that protein expression is modulated by dietary Mg2+. In particular, Mg2+ restriction upregulated TRPM6 expression, while Mg2+ supplementation resulted in a significant decrease in protein levels. This work confirms and extends our previous results on TRPM6 modulation by Mg2+ availability in mammary tissues. Further studies are required to clarify the functional significance of these findings, and the role of TRPM6 in tissue-specific magnesium homeostasis.