Transsarcolemmal sodium-calcium exchange and myocardial oxygen consumption in isolated rat ventricular myocytes

We studied oxygen consumption and energy metabolism in isolated rat ventricular myocytes which were subjected to an abrupt change in the cation composition of the extracellular medium ('transition'); extracellular [Na+] was decreased either alone or in combination with a change of [K+] or [Ca2+]. The magnitude of change of the cation concentration(s) was varied. The respiratory rate (vO2) of myocytes changed biphasically after such a transition. vO2 increases to a maximum after about 25 to 30 s and returns to almost control after 180 to 200 s. vO2-max depends on both the nature of the cation(s) of which the concentration(s) are varied and on the magnitude of these change(s); vO2-max can almost be as high as that induced by uncoupling of oxidative phosphorylation with DNP. The free energy of hydrolysis of cytoplasmic ATP hardly decreases after transition. Cell viability remains unaltered, although an increasingly larger fraction of rod-shaped cells transform to a hypercontracted state with increasing magnitude of the extracellular ion concentration change. Reversal of the ionic change or addition of EGTA at 30 s after transition accelerates the return of vO2 to the value prior to transition. In the presence of ouabain, vO2-max is higher and return to control is slower and incomplete. The total amount of oxygen consumption after transition, is linearly related to the initial change of the free energy of the Na+/Ca(2+)-exchanger caused by the cation concentration change(s); this relationship does not depend on the nature of the cation(s) changed. We conclude that the transient increase of vO2 after transition is regulated by intracellular free [Ca2+], which transiently increases. This transient increase is caused by change of the thermodynamic driving force on the Na+/Ca(2+)-exchanger after transition.