MITOCHONDRIAL F1-ATPASE ACTIVITY OF CANINE MYOCARDIUM - EFFECTS OF HYPOXIA AND STIMULATION

Recent studies have suggested that modifications in mitochondrial F-1-adenosinetriphosphatase (ATPase) activity may play an important role in the regulation of myocardial oxidative phosphorylation. The goal of the present study was to develop and characterize an assay of F-1-ATPase activity that could be performed repeatedly on an intact heart under various physiological states. With the use of submitochondrial particles prepared from biopsy samples of canine myocardium, we found reproducible F-1-ATPase activity when normalized to the activity of the intramitochondrial enzyme citrate synthase. The oligomycin-sensitive component of the ATPase activity was found to be mainly F-1-ATPase. F-1-ATPase activity of normal myocardium increased by incubation in high salt-pH buffer, suggesting baseline inhibition. Five minutes after global ischemia, F-1-ATPase activity decreased to 60% of baseline. Hypoxia for 10 min resulted in no significant change in F-1-ATPase activity. With phenylephrine infusion, myocardial oxygen consumption more than doubled, whereas F-1-ATPase activity increased by similar to 30%. Both returned to baseline levels after discontinuation of the drug. With the use of an assay developed to measure F-1-ATPase activity of intact myocardium, changes of the enzyme activity were found during both ischemia and at increased work loads. These data suggest that alterations of F-1-ATPase activity may contribute to the regulation of myocardial oxidative phosphorylation.