Effects of oligomycin and acidosis on rates of ATP depletion in ischemic heart muscle.
The perfusion of canine cardiac muscle with 10 microM oligomycin produced a nearly 90% slowing of the net rate of tissue ATP depletion from 0.200 to 0.025 mumol X min-1 X g wet wt-1 of tissue during a subsequent myocardial autolytic interval during which tissue pH was held constant. Moreover, lowering the tissue pH during the autolytic process by 0.6 unit from approximately 6.8 to approximately 6.2 produced a nearly 60% slowing of the net rate of tissue ATP depletion from 0.200 to 0.087 mumol X min-1 X g wet wt-1. The pH dependence of the net rate of tissue ATP depletion (by an oligomycin-sensitive process) was that predicted from the mitochondrial ATPase pH-inhibition profiles reported earlier (J. Biol. Chem. 258: 9657-9661, 1983). When taken together with our observation that the mitochondrial ATPase comprises approximately 90% of the total of all of the ATP hydrolyzing activities present in cardiac muscle cells, data reported here suggest that the protonic inhibition of the mitochondrial ATPase plays a major role in regulating the rate of tissue ATP depletion during myocardial ischemia.
D000138:Acidosis / Q000378:metabolism*; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001329:Autolysis / Q000201:enzymology / Q000378:metabolism; D003327:Coronary Disease / Q000378:metabolism*; D004285:Dogs; D005260:Female; D006531:HEPES / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D008297:Male; D008929:Mitochondria, Heart / Q000201:enzymology; D009206:Myocardium / Q000378:metabolism*; D009210:Myofibrils / Q000201:enzymology; D009840:Oligomycins / Q000494:pharmacology*
D009840:Oligomycins; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases; D006531:HEPES