Exacerbation of the calcium paradox with exogenous adenosine triphosphate in isolated working rat heart

The deleterious effect of calcium withdrawal and restoration on cardiac cell membranes ('Ca-paradox') was studied using isolated, working rat heart. The optical density of the coronary sinus effluent was measured at 260 nm wavelength. The efflux of A260 material upon restoration of calcium was proportional to the duration of calcium-free perfusion, indicating graded membraneous injury. When ATP, 10(-6) to 10(-4) M, was added to the calcium-free perfusate for 30 s of calcium-free perfusion, release of A260 material increased as a logarithmic function of exogenous ATP concentration. That this exacerbating effect is produced by such low concentrations relative to intracellular amounts indicates an action of ATP on the membrane surface. It is suggested that exogenous ATP enhances calcium entry into the cell, thus contributing to calcium influx through membranes already rendered abnormally permeable from the 'Ca-paradox' mechanism.