Abstract
Ion channels are specialized proteins that span the plasma membrane of living cells allowing ion fluxes through this essentially impermeable barrier. Most ion channels show selectivity in that their pores are more permeable to some ions than to others. The development of the patch-clamp technique enabled the researcher for the first time to monitor in real-time the activity of ion channels in the plasma membrane. The TRP (Transient Receptor Potential) family consists of ion channels with structural similarities. TRP proteins are widely expressed in organisms and contribute to diverse functions and processes ranging from thermal, tactile or taste sense to transepithelial calcium and magnesium transport. The epithelial calcium channels TRPV5 and TRPV6 represent two highly homologous members of the TRP family that are mainly expressed in calcium-transporting epithelia. TRPV5 plays the role of gatekeeper for renal calcium reabsorption while TRPV6 forms the main calcium influx pathway in the small intestine. The epithelial magnesium channel TRPM6 constitutes the magnesium entry gate for transepithelial magnesium transport. TRPM6 shares with its closest homologue, TRPM7, beside their exceptional magnesium permeability, the presence of an atypical a- kinase in the carboxyl-terminal domain. A tight regulation of the epithelial calcium and magnesium channels is of particular physiological importance for maintaining the body balance of these divalent ions. Therefore, the living organisms are equipped with an efficient feedback homeostatic system capable of maintaining the extracellular concentrations of these ions between narrow limits. Therefore, the general goal of this thesis was to get further insight into the physiological and molecular regulation of epithelial calcium and magnesium channels in order to ultimately understand the transcellular transport of these divalent cations.
