The Squid Preparation as a General Model for Ionic and Metabolic Na + /Ca 2+ Exchange Interactions: Physiopathological Implications

• Published in: Annals of the New York Academy of Sciences 2007-03, Vol.1099 (1), p.135-151
• Main Authors: DIPOLO, R., BEAUGÉ, L.
• Format: Article
• Language: English
• ISSN: 0077-8923; 1749-6632
• DOI: 10.1196/annals.1387.049

We propose an integrated kinetic model for the squid nerve Na + /Ca 2+ exchanger based on experimental evidences obtained in dialyzed axons. This model satisfactorily explains the interrelationship between ionic (Na + i –H + i –Ca 2+ i ) and metabolic (ATP, phosphoarginine (PA)) regulation of the exchanger. Data in dialyzed axons show that the Ca i ‐regulatory site located in the large intracellular loop plays a central role in the modulation by ATP by antagonizing the inhibitory Na + i –H + i synergism. We have used the Na o /Na i exchange mode to unequivocally measure the affinity of the Ca i ‐regulatory site. This allowed us to separate Ca i ‐regulatory from Ca i ‐transport sites and to estimate their respective affinities. In this work we show for the first time that under conditions of saturation of the Ca i ‐regulatory site (10 μM Ca 2+ i , pH i 8.0), ATP have no effect on the Ca i ‐transport site. In addition, we have expanded our equilibrium kinetic model of ionic and metabolic interactions to a complete exchange cycle (circular model). This model, in which the Ca i ‐regulatory site plays a central role, accounts for the decrease in Na i inactivation, at high pH i , high Ca 2+ i, and MgATP. Furthermore, the model also predicts the net Ca 2+ movements across the exchanger based on the exchanger complexes redistribution both during physiological and pathological conditions (ischemia).