Vol. 280, Issue 4, R1221-R1229, April 2001
Metabolic consequences of a species difference in Gibbs free
energy of Na+/Ca2+ exchange: rat versus guinea
pig
P. J.
Cooper,
M.-L.
Ward,
P. J.
Hanley,
G. R.
Denyer, and
D. S.
Loiselle
Department of Physiology, Faculty of Medicine and Health
Science, University of Auckland, Private Bag 92019, Auckland, New
Zealand
The Gibbs free energy of the sarcolemmal
Na+/Ca2+ exchanger (
GNa/Ca)
determines its net Ca2+ flux. We tested the hypothesis that
a difference of diastolic GNa/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
GNa/Ca by reduction of extracellular Na+
concentration, [Na+]o. Hill equations fitted
to the resulting
VO2-[Na+]o
relationships yielded Michaelis constant (Km)
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 Km values to a 7.84 kJ/mol
difference of GNa/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.
myocardial oxygen consumption; intracellular Ca2+,
cardiac energetics; K+ arrest; verapamil arrest
