AJP - Cell Physiology, Vol 262, Issue 5 C1297-C1303, Copyright © 1992 by American Physiological Society
Mitochondrial ATP-synthase activity in cardiomyocytes after aerobic-anaerobic metabolic transition
T. Noll, A. Koop and H. M. Piper
Physiologisches Institut I, Universitat Dusseldorf, Federal Republic of Germany.
It has been hypothesized that, in oxygen-depleted myocardial cells,
mitochondria are depolarized and the F1,F0-proton adenosinetriphosphatase
(ATPase) catalyzes net ATP hydrolysis when the cells exhibit the signs of
an aerobic-anaerobic metabolic transition, which are increased lactate
formation and decline in high-energy phosphate reserves [W. Rouslin, C. W.
Broge, and I. L. Grupp. Am. J. Physiol. 259 (Heart Circ. Physiol. 28):
H1759-H1766, 1990]. This hypothesis was tested by incubating isolated
cardiomyocytes from the adult rat in substrate-free Tyrode solution (37
degrees C, pH 7.4) at a PO2 less than or equal to 0.1 Torr, i.e.,
1,000-fold below the normal arterial level. At this deep hypoxia, the
following results were found. 1) Lactate production was activated to
maximal rates and high-energy phosphate contents decreased
(aerobic-anaerobic metabolic transition). The inhibitor of the
mitochondrial F1,F0-proton ATPase oligomycin, however, added upon
establishment of hypoxia, did not slow down, as in the case of depolarized
mitochondria, but moderately accelerated energy depletion. 2) Activation of
mitochondrial ATP hydrolysis could be provoked in these hypoxic cells by
addition of cyanide, antimycin A, and rotenone, i.e., specific inhibitors
of certain sites of the respiratory chain. The enhancement of loss of ATP
could be inhibited by oligomycin. The results demonstrate that states of
deep hypoxia of the cardiomyocyte are possible in which it undergoes an
aerobic-anaerobic metabolic transition, indicated by increased lactate
formation and progressive loss of cellular energy reserves, and yet
mitochondrial ATPase hydrolytic activity is not activated.
