Glycolytic oscillations in single ischemic cardiomyocytes at near anoxia.
Previous studies have shown that oscillations of the metabolism can occur in cardiomyocytes under conditions simulating ischemia/reperfusion. It is not known whether they can also occur during real ischemia with near-anoxic oxygen tension. Here, using oxygen clamp in on-chip picochambers, we exposed single resting cardiomyocytes to near anoxia (pO(2) < 0.1 mm Hg). We show that at near anoxia, the mitochondrial membrane potential (DeltaPsi) was kept by the F(1)F(0)-ATPase reversal, using glycolytic adenosine triphosphate (ATP). In many cells, activation of current through sarcolemmal K(ATP) channels (I(KATP)) started after a delay with one or several oscillations (frequency of 0.044 +/- 0.002 Hz). These oscillations were time correlated with oscillations of DeltaPsi. Metabolic oscillations at near anoxia are driven by glycolysis because (a) they were inhibited when glycolysis was blocked, (b) they persisted in cells treated with cytoplasmic reactive oxygen species scavengers, and (c) the highest rate of ATP synthesis during an oscillation cycle was associated with the generation of reducing equivalents. Glycolytic oscillations could be initiated upon rapid, but not slow, transition to near anoxia, indicating that the speed of ATP/ADP ratio drop is a determinant of their occurrence. At enhanced oxidative stress, the rate of ATP consumption was increased as indicated by rapid I(KATP) activation with large-scale oscillations. These results show that metabolic oscillations occur in cardiomyocytes at near anoxia and are driven by glycolysis and modulated by mitochondria through the rate of ATP hydrolysis, which, in turn, can be accelerated by oxidative stress.
Department of Physiology II, University of Jena, Jena, Germany.
Vladimir
V
Ganitkevich
Violeta
V
Mattea
Klaus
K
Benndorf
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001683:Biological Clocks; D002478:Cells, Cultured; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis; D051379:Mice; D008955:Models, Cardiovascular; D017202:Myocardial Ischemia / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism*
D000255:Adenosine Triphosphate; D005947:Glucose; D010100:Oxygen