INIMEC - CONICET   05467
INSTITUTO DE INVESTIGACION MEDICA MERCEDES Y MARTIN FERREYRA
Unidad Ejecutora - UE
artículos
Título:
Ionic interactions with the Sodium-Calcium exchanger. Modulation by ATP
Autor/es:
DIPOLO, R., ELSO DE BERBEIRÁN G., ROJAS, H., RAIMUNDA, D., DELGADO, D. AND BEAUGÉ, L.
Revista:
Physiological Mini-Reviews On line
Editorial:
Edited by the Argentine Physiological Society
Referencias:
Lugar: Buenos Aires; Año: 2007 vol. 1 p. 1 - 18
Resumen:
The last decade has witnessed a marked increased in studies on the Na+/Ca2+ exchanger, driven mainly by its likely implications in physiological and patho-physiological processes at cellular and organic levels. Key areas of these studies include molecular biology, electrophysiology and actual measurements of radioactive labeled Na+ and Ca2+. In all cases the emphasis was put on the regulation of the exchanger.  There are three main types of regulations that take place at the large intracellular loop of the exchanger protein: (i) Ionic (sodium inactivation, calcium regulation and proton-inhibition); (ii) Metabolic (ATP and, in the squid, phosphoarginine); and (iii) Genetic (alternative splicing). This review analyzes the most recent data on the mutual interactions of regulatory ionic ligands (Ca2+, Na+, H+) and the way they secondarily modulated by MgATP. The emphasis is put on the importance of the binding of Ca2+ to its regulatory site as an essential requirement for the exchange function. Intracellular protons and sodium inhibit Na+/Ca2+ exchanger by reducing the apparent affinity of the Cai-regulatory site for Ca2+. Although the metabolic pathways are different in the mammalian heart (membrane polyphosphoinositides) and squid nerve cells (soluble cytosolic regulatory protein), the final target for the protective effect of MgATP is the same in both cases: a reduction of Na+i-H+i binding affinities facilitating the attachment of Ca2+ to its regulatory site. Early kinetic models which partially analyzed some of these interactions where integrated into a single scheme with the Cai-regulatory site playing a central role.