Interplay of Ca2+ and Mg2+ in Sodium-Calcium exchanger and in other Ca2+-binding proteins: Magnesium, watchdog that blocks each turn if able

Abstract

Sodium-calcium exchange across plasma membrane is regulated by intracellular calcium ions. The sodium-calcium exchanger (NCX1) is activated by successive saturation of numerous Ca2+-binding sites located in the intracellular loop of the protein. The progressive saturation of the binding domain CBD12 by Ca2+ results in a series of conformational changes of CBD12 as well as of entire NCX1 molecule. Like other soluble and membrane Ca2+-binding proteins, NCX1 can also be regulated by Mg2+ that antagonises Ca2+ at the level of divalent cation-binding sites. This chapter summarises data on Mg2+ impacts in the cells. Regulatory action of Mg2+ on intracellular Ca2+-dependent processes can be achieved due to changes of its cytoplasmic level, which take place in the range of [Mg2+]i from 0.5 to 3 mM. Under normal conditions, these changes are ensured by activation of plasmalemmal Mg 2+ transport systems and by variations in ATP level in cytoplasm. In heart and in brain, some pathological conditions, such as hypoxia, ischemia and ischemia followed by reperfusion, are associated with an important increase in intracellular Ca2+. The tissue damage due to Ca2+ overload may be prevented by Mg2+. The protective actions of Mg2+ can be achieved due to its ability to compete with Ca2+ for the binding sites in a number of proteins responsible for the rise in intracellular free Ca2+, including NCX1, in case when the reverse mode of Na +/Ca2+ exchange becomes predominant. Saturation of CBD12 by Mg2+ results in important changes of NCX1 conformation. Modulating actions of Mg2+ on the conformation of NCX1 were detected at a narrow range of Mg2+ concentration, from 0.5 to 1 mM. These data support an idea that variations of intracellular Mg2+ could modify transmembrane Ca2+ movements ensured by NCX1. © Springer Science+Business Media New York 2013.