Sodium/Calcium exchanger: Influence of Matabolic Regulation on Ion Carrier Interactions,

REINALDO DIPOLO Y LUIS BEAUGÉ

Physiological Reviews

Americal Physiological Society

Lugar: Bethesda, Maryladn, USA; Año: 2006 vol. 86 p. 155 - 203

0031-9333

The Na+/Ca2+ exchangers’ family of membrane transporters is ubiquity distributed in cells and tissues of the animal kingdom and constitutes one of the most important mechanisms for extruding Ca2+ from the cell. Two basic properties characterize them: 1-Their activity is not predicted by thermodynamic parameters of classical electrogenic counter-transporters (dependence on ionic gradients and membrane potential), but is markedly regulates by transported (Na+ and Ca2+) and non-transported ionic species (protons and other monovalent cations). These modulations take place at specific sites in the Na+/Ca2+ exchanger protein located at extra, intra and trans-membrane protein domains. 2- Exchange activity is also regulated by the metabolic state of the cell. The mammalian and invertebrate preparations share MgATP in that role; the squid has an additional compound, phosphoarginine. This review emphasizes the interrelationships between ionic and metabolic modulations of Na+/Ca2+ exchange, focusing mainly in two preparations where most of the studies have been carried out: the mammalian heart and the squid giant axon. A surprising fact that emerges when comparing the MgATP related pathways in these two systems is that although they are different (PIP2 in the cardiac and  a soluble cytosolic regulatory protein in the squid), their final target effects are essentially similar: Na+-Ca2+-H+ interactions with the exchanger,. A model integrating both ionic and metabolic interactions in the regulation of the exchanger is discussed in detail as well as its relevance in cellular Ca2+i homeostasis.