Cellular energy utilization and supply during hypoxia in embryonic cardiac myocytes.
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 with the value obtained at an oxygen tension (PO2) of 120 Torr, cellular O2 uptake decreased by 28 +/- 14% (SD) at PO2 = 50 Torr and by 64 +/- 25% at PO2 = 20 Torr (P < 0.05). This decrease was similar after 1 min or 2 h of hypoxia, was sustained for 16 h, 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 myocytes adherent to glass cover-slips, O2 uptake and contractile motion were decreased after 30-60 min at 50 and 20 Torr, compared with normoxic values. O2 uptake also was significantly decreased at 50 and 20 Torr in myocytes incubated with 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.
Budinger
G R
GR
University of Chicago, Illinois 60637, USA.
Chandel
N
N
Shao
Z H
ZH
Li
C Q
CQ
Melmed
A
A
Becker
L B
LB
Schumacker
P T
PT
D000208:Acute Disease; D000227:Adenine Nucleotides / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000693:Anaerobiosis; D000818:Animals; D002448:Cell Adhesion; D002642:Chick Embryo; D004734:Energy Metabolism; D006019:Glycolysis; D000860:Hypoxia / Q000378:metabolism* / Q000473:pathology*; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009994:Osmolar Concentration; D010101:Oxygen Consumption / Q000187:drug effects; D010725:Phosphocreatine / Q000378:metabolism; D013772:Tetramethylphenylenediamine / Q000494:pharmacology
D000227:Adenine Nucleotides; D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D013772:Tetramethylphenylenediamine