TRPM6 and TRPM7 Chanzymes Essential for Magnesium Homeostasis

Mg2+ is the second most abundant intracellular cation and plays an essential role as cofactor in many enzymatic reactions. Regulation of the total body Mg2+ balance principally resides within the kidney that tightly matches the intestinal absorption of Mg2+. The identification of epithelial Mg2+ transporters in the kidney has been greatly facilitated by studying hereditary disorders with primary hypomagnesemia. Identification of the gene defect in hypomagnesemia with secondary hypocalcemia has recently elucidated the TRPM6 protein, a member of the transient receptor potential melastatin (TRPM) family. TRPM6 shows the highest homology with TRPM7, which has been identified as a Mg2+-permeable ion channel primarily required for cellular Mg2+ homeostasis. TRPM6 and TRPM7 are distinct from all other ion channels b ecause t hey are composed of a channel linked to a protein kinase domain and therefore referred to as chanzymes. These chanzymes are essential for Mg2+ homeostasis, which is critical for human health and cell viability. This chapter d escribes the characteristics of epithelial Mg2+ transport in general and highlights the distinctive features and the physiological relevance of these new chanzymes in (patho)physiological situations.