Cellular energy utilization and supply during hypoxia in embryonic
cardiac myocytes.
Budinger, G. R. Scott, Navdeep Chandel, Z. H. Shao, C. Q. Li, Ari
Melmed, Lance B. Becker, and Paul T. Schumacker.
Pulmonary and Critical Care Medicine, The University of Chicago,
Chicago, Illinois
APStracts 2:0133L, 1995.
Studies of intact hearts suggest that cardiac myocytes may have the
ability to reversibly suppress metabolic activity and energy demand
in states of regional hypoperfusion. However, an ability to suppress
respiration in response to hypoxia has never been demonstrated in
isolated myocytes. To test this, isolated embryonic chick cardiac
myocytes were exposed to progressive hypoxia while their rate of O2
uptake and concentrations of lactate, ATP, ADP, AMP and
phosphocreatine were measured. Compared to the value obtained at an
oxygen tension (PO2) of 120 torr, cellular O2 uptake decreased by 28
+/- 14 % (S.D.) at PO2 = 50 torr, and 64 +/- 25 % at PO2 = 20 torr
(p<0.05). This decrease was similar after 1 min or 2 hr of
hypoxia, was sustained for 16 hours, and was completely reversible
within 2 min after reoxygenation. The reduction in O2 uptake was
associated with a decrease in the rate of ATP turnover, but no change
in adenine nucleotide or phosphocreatine concentrations. In myocyt es
adherent to glass coverslips, O2 uptake and contractile motion were
decreased after 30-60 min at 50 and 20 torr, compared with normoxic
values. Oxygen uptake also was significantly decreased at 50 and 20
torr in myocytes incubated with TMPD (N,N,N',N'-tetramethyl-p
-phenylenediamine), which suggests that the catalytic activity of
cytochrome c oxidase was partially inhibited during hypoxia. In
summary, these results demonstrate that embryonic chick cardiac
myocytes can suppress their rates of ATP demand, ATP utilization and
O2 uptake during moderate hypoxia, through a mechanism that involves
a reversible inhibition of cytochrome c oxidase. This mechanism may
represent a protective response to cellular hypoxia.
Received 13 January 1995; accepted in final form 24 July 1995.
APS Manuscript Number L12-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 14 August 1995.