Molecular basis of epithelial Ca2+ and Mg2+ transport: insights from the TRP channel family

Abstract

Maintenance of plasma Ca(2+) and Mg(2+) levels is of vital importance for many physiological functions. This is achieved via a coordinated interplay between the intestine, bone and kidney by amending the rate of absorption, storage and excretion, respectively. Discovery of the transient receptor potential (TRP) family identified several new ion channels acting as gatekeepers of Ca(2+) and Mg(2+) transport in these epithelia, greatly increasing our understanding of the molecular processes that facilitate the movement of these minerals. In the intestine, TRP channels contribute to the saturable active transcellular movement of divalent cations from the lumen into the enterocyte. Furthermore, in bone, TRPV channels play important roles by influencing the osteoclastic resorption process, thereby contributing importantly to overall bone mineral content. The divalent cation-permeable TRPV5 and TRPM6 channels are located in the renal distal convolution, the main site of active transcellular Ca(2+) and Mg(2+) transport. The channels are regulated by a multitude of factors and hormones that contribute importantly to keeping the systemic concentrations of Ca(2+) and Mg(2+) within normal limits. Dysregulation of either channel impacts the renal reabsorptive capacity for these cations. This review summarizes the current knowledge related to TRP channels in epithelial Ca(2+) and Mg(2+) transport.