Reversible ischemic inhibition of F1F0-ATPase in rat and human myocardium

The physiological role of F1F0-ATPase inhibition in ischemia may be to reta rd ATP depletion although views of the significance of IF1 are at variance. We corroborate here a method for measuring the ex vivo activity of F1F0-AT Pase in perfused rat heart and show that observation of ischemic F1F0-ATPas e inhibition in rat heart is critically dependent on the sample preparation and assay conditions, and that the methods can be applied to assay the isc hemic and reperfused human heart during coronary by-pass surgery. A 5-min p eriod of ischemia inhibited F1F0-ATPase by 20% in both rat and human myocar dium. After a 15-min reperfusion a subsequent 5-min period of ischemia doub led the inhibition in the rat heart but this potentiation was lost after 12 0 min of reperfusion. Experiments with isolated rat heart mitochondria show ed that ATP hydrolysis is required for effective inhibition by uncoupling. The concentration of oligomycin for 50% inhibition (I-50) for oxygen consum ption was five times higher than its I-50 for F1F0-ATPase. Because of the d ifferent control strengths of F1F0-ATPase in oxidative phosphorylation and ATP hydrolysis an inhibition of the F1F0-ATPase activity in ischemia with t he resultant ATP-sparing has an advantage even in an ischemia/reperfusion s ituation. (C) 2001 Elsevier Science B.V. All rights reserved.