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

Abstract

The Gibbs free energy of the sarcolemmal Na+/Ca2+ exchanger (ΔGNa/Ca) determines its net Ca2+ flux. We tested the hypothesis that a difference of diastolic ΔGNa/Ca exists between rat and guinea pig myocardium. We measured the suprabasal rate of oxygen consumption (Vo 2) of arrested Langendorff-perfused hearts of both species, manipulating ΔGNa/Ca by reduction of extracellular Na+concentration, [Na+]o. Hill equations fitted to the resulting Vo 2-[Na+]orelationships 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 ΔGNa/Ca. The model predicts that reversal of Na+/Ca2+ exchange, leading to diastolic Ca2+ influx, should occur at a value of [Na+]o 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°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.