Epithelial Ca2+ and Mg2+ channels in health and disease

A near constancy of the extracellular Ca2+ and Mg2+ concentration is required for numerous physiologic functions at the organ, tissue, and cellular levels. This suggests that minor changes in the extracellular concentration of these divalents must be detected to allow the appropriate correction by the homeostatic systems. The maintenance of the Ca2+ and Mg2+ balance is controlled by the concerted action of intestinal absorption, renal excretion, and exchange with bone. After years of research, rapid progress was made recently in identification and characterization of the Ca2+ and Mg2+ transport proteins that contribute to the delicate balance of divalent cations. Expression-cloning approaches in combination with knockout mice models and genetic studies in families with a disturbed Mg2+ balance revealed novel Ca2+ and Mg2+ gatekeeper proteins that belong to the super family of the transient receptor potential (TRP) channels. These epithelial Ca2+ (TRPV5 and TRPV6) and Mg2+ channels (TRPM6 and TRPM7) form prime targets for hormonal control of the active Ca2+ and Mg2+ flux from the urine space or intestinal lumen to the blood compartment. This review describes the characteristics of epithelial Ca2+ and Mg2+ transport in general and highlights in particular the distinctive features and the physiologic relevance of these new epithelial Ca2+ and Mg2+ channels in (patho)physiologic situations.