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 i n the regulation of myocardial oxidative phosphorylation. The goal of the present study was to develop and characterize an assay of F-1-ATPa se activity that could be performed repeatedly on an intact heart unde r various physiological states. With the use of submitochondrial parti cles prepared from biopsy samples of canine myocardium, we found repro ducible F-1-ATPase activity when normalized to the activity of the int ramitochondrial enzyme citrate synthase. The oligomycin-sensitive comp onent of the ATPase activity was found to be mainly F-1-ATPase. F-1-AT Pase activity of normal myocardium increased by incubation in high sal t-pH buffer, suggesting baseline inhibition. Five minutes after global ischemia, F-1-ATPase activity decreased to 60% of baseline. Hypoxia f or 10 min resulted in no significant change in F-1-ATPase activity. Wi th phenylephrine infusion, myocardial oxygen consumption more than dou bled, whereas F-1-ATPase activity increased by similar to 30%. Both re turned to baseline levels after discontinuation of the drug. With the use of an assay developed to measure F-1-ATPase activity of intact myo cardium, changes of the enzyme activity were found during both ischemi a and at increased work loads. These data suggest that alterations of F-1-ATPase activity may contribute to the regulation of myocardial oxi dative phosphorylation.