Metabolic consequences of a species difference in Gibbs free energy of Na+/Ca2+ exchange: rat versus guinea pig.

The Gibbs free energy of the sarcolemmal Na+/Ca2+ exchanger (DeltaG(Na/Ca)) determines its net Ca2+ flux. We tested the hypothesis that a difference of diastolic DeltaG(Na/Ca) exists between rat and guinea pig myocardium. We measured the suprabasal rate of oxygen consumption (VO2) of arrested Langendorff-perfused hearts of both species, manipulating DeltaG(Na/Ca) by reduction of extracellular Na+ concentration, Na+. Hill equations fitted to the resulting VO2-Na+ relationships yielded Michaelis constant (K(m)) values of 67 and 25 mM for rat and guinea pig, respectively. We developed and tested a simple thermodynamic model that attributes this difference of K(m) values to a 7.84 kJ/mol difference of DeltaG(Na/Ca). The model predicts that reversal of Na+/Ca2+ exchange, leading to diastolic Ca2+ influx, should occur at a value of Na+ about three times higher in rat myocardium. We verified this quantitative prediction using fura 2 fluorescence to index intracellular Ca2+ concentration in isolated ventricular trabeculae at 37 degrees C. The postulated difference in free energy of Na+/Ca2+ exchange explains a number of reported disparities of Ca2+ handling at rest between rat and guinea pig myocardia.