Sodium/Calcium Exchanger: Influence of Metabolic Regulation on Ion Carrier Interactions

Abstract

The Na+/Ca2+ exchanger's family of membrane transporters is widely 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 countertransporters (dependence on ionic gradients and membrane potential), but is markedly regulated by transported (Na+ and Ca2+) and nontransported ionic species (protons and other monovalent cations). These modulations take place at specific sites in the exchanger protein located at extra-, intra-, and transmembrane 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 (phosphatidylinositol bisphosphate 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 Cai2+ homeostasis.

Age-Dependent Brain Tissue Hydration, Ca Exchange and their Dose- Dependent Ouabain Sensitivity

“…It is well known that anesthetics with different chemical and pharmacological profiles [31][32][33] significantly affect metabolic processes which play an important role in regulation of cell volume [12,34]. Therefore, in present experiments the animals were sharply immobilized by freezing method (dipping their noses into liquid nitrogen for 3-4 sec) and decapitated [35].…”

“…It is known that Ca ions can be removed from cells by two mechanisms: Ca-pump and Na + /Ca 2+ exchange in forward mode. Notwithstanding the affinity of Ca-pump is higher than Na + /Ca 2+ exchange because the latter has incomparably higher rate than Ca-pump, it is suggested that Na + /Ca 2+ exchange has a more essential role in regulation of [Ca] i homeostasis [12,34]. There is a great number of literature data about the crucial role of α 3, α 2 isoforms of Na + /K + in regulation of Na + /Ca 2+ exchange.…”

El acoplamiento excitación-contracción en el músculo esquelético: preguntas por responder a pesar de 50 años de estudio

“…Se ha aceptado que la relajación de la fibra muscular esquelética es consecuencia de la activación de la SERCA del retículo sarcoplásmico y de la unión del Ca 2+ a la parvalbúmina. Sin embargo, en los últimos años se ha propuesto la participación de las mitocondrias y del intercambiador Na + -Ca 2+ en este proceso, ya que ambos se encuentran involucrados en la regulación de la homeostasis de Ca 2+ en otros tipos celulares, excitables y no excitables (157).…”

Kinetic and Equilibrium Properties of Regulatory Calcium Sensors of NCX1 Protein

“…The NCX proteins are regulated by cytosolic Na ϩ and Ca 2ϩ (10 -13). A rise in Na ϩ rapidly stimulates and then inactivates the exchanger, whereas cytosolic Ca 2ϩ activates NCX1 and relieves the Na ϩ -dependent inactivation (11)(12)(13)(14)(15)(16). The alternative splicing of NCX1 dramatically alters the relationships between Na ϩ -dependent and Ca 2ϩ -dependent regulation (12)(13)(14).…”