Sodium-calcium exchange stoichiometry: is the noose tightening?

The stoichiometry of cardiac sodium-calcium exchange is of profound importance to understanding its physiological function, and recent work challenges a simple 3-to-1 stoichiometry. We present a refined 3-to-1 exchange model that can explain recently measured reversal potentials that are close to those expected for a 4-to-1 exchanger. The model assumes that 1 calcium and 1 sodium ion can be transported by the exchanger, albeit more slowly than 3 sodium ions or 1 calcium ion. In this model, currents and calcium fluxes reverse at different potentials; resting free calcium would always be higher than expected for a perfect 3-to-1 exchange process. To test models such as this, we have developed new methods to study ion transport processes in giant membrane patches independent of, or in parallel with, current measurements. Briefly, ion-selective electrodes or fluorescent ion indicators are used to detect concentration changes in the pipette, close to the membrane, upon activation of transport activity. Preliminary results are presented.