Dual effect of Nai+ on Ca2+ influx through the Na+/Ca2+ exchanger in dialyzed squid axons

BEAUGÉ, L. AND DIPOLO, R.

AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY

Año: 2008 vol. 294 p. 118 - 125

0363-6143

We propose a steady state kinetic model for the squid Na+/Ca2+ exchanger which differs from other current models of regulation in that it takes into account within a single kinetic scheme all ionic (Ca2+i- Na+i-H+i) and metabolic (ATP) regulations of the exchanger in which the Cai-regulatory plays the central role in regulation. Although the integrated ionic-metabolic model predicts all squid steady-state experimental data on exchange regulation, a critical test for the validity of it is the predicted dual effect of Na+i on the steady-state Ca2+ influx through the exchanger. To test this prediction, an improved technique for estimating of isotope fluxes in squid axons was developed which allows sequential measurements of ion influx and effluxes. With this method we report here two novel observations of the squid axon Na+/Ca2+ exchanger: (i) At pHi (7.0) and in the absence of MgATP, intracellular Na+ has a dual effect on Ca2+ influx: inhibition at low concentrations followed by stimulation at high [Na+]i. reaching levels higher than those seen without Na+i; (ii) In the presence of MgATP, the biphasic response to Na+i disappears and is replaced by a sigmoid activation. Furthermore, the model predicts that Ca2+ efflux is monotonically inhibited by Na+i, more pronouncedly without than with MgATP. These results are predicted by the proposed kinetic model. Although not fully applicable to all exchangers, this scheme might provide some insights on expected net Ca2+ movements in other tissues under a variety of intracellular ionic and metabolic conditions.