The squid preparation as a general model for ionic and metabolic Na+/Ca2+ exchange interactions: physiopathological implications.
We propose an integrated kinetic model for the squid nerve Na+/Ca2+ exchanger based on experimental evidences obtained in dialyzed axons. This model satisfactorily explains the interrelationship between ionic (Na+(i)-H+(i)-Ca2+(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 microM Ca2+(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 Ca2+(i,) and MgATP. Furthermore, the model also predicts the net Ca2+ movements across the exchanger based on the exchanger complexes redistribution both during physiological and pathological conditions (ischemia).
DiPolo
R
R
Laboratorio de Fisiología Celular, Centro de Biofísica y Bioquímica, IVIC, Apartado 21827, Caracas 10020-A, Venezuela. dipolor@ivic.ve
Beaugé
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L
D000818:Animals; D002118:Calcium / Q000378:metabolism; D049832:Decapodiformes; D007700:Kinetics; D008962:Models, Theoretical; D019831:Sodium-Calcium Exchanger / Q000378:metabolism*
D019831:Sodium-Calcium Exchanger; D002118:Calcium