PMID- 10516172
OWN - NLM
STAT- MEDLINE
DCOM- 19991117
LR  - 20180927
IS  - 0002-9513 (Print)
IS  - 0002-9513 (Linking)
VI  - 277
IP  - 4
DP  - 1999 Oct
TI  - Dynamic adaptation of cardiac oxidative phosphorylation is not mediated by simple 
      feedback control.
PG  - H1375-84
LID - 10.1152/ajpheart.1999.277.4.H1375 [doi]
AB  - The classic idea about regulation of cardiac oxidative phosphorylation (OxPhos) 
      was that breakdown products of ATP (ADP and P(i)) diffuse freely to the 
      mitochondria to stimulate OxPhos. On the basis of this metabolic feedback control 
      system, the response time of OxPhos (t(mito)) is predicted to be inversely 
      proportional to the mitochondrial aerobic capacity (MAC). We determined t(mito) 
      during steps in heart rate in isolated perfused rabbit hearts (n = 16) before and 
      after reducing MAC with nonsaturating doses of oligomycin. The reduction of MAC 
      was quantified in mitochondria isolated from each perfused heart, dividing 
      oligomycin-sensitive, ADP-stimulated state 3 respiration by 
      oligomycin-insensitive uncoupled respiration. The t(mito) to heart rate steps 
      from 60 to 70 and 80 beats/min was 5. 6 +/- 0.6 and 7.2 +/- 0.8 s (means +/- SE) 
      and increased an estimated 34 and 40% for a 50% decrease in MAC (P < 0.05), 
      respectively, which is much less than the 100% predicted by the feedback 
      hypothesis. For steps to 100 or 120 beats/min, t(mito) was 8.3 +/- 0.5 and 11.2 
      +/- 0.6 s and was not reduced with decreases in MAC (P > 0.05). We conclude that 
      immediate feedback control by quickly diffusing ADP and P(i) cannot explain the 
      dynamic regulation of cardiac OxPhos. Because calcium entry into the mitochondria 
      also cannot explain the first fast phase of OxPhos activation, we propose that 
      delay of the energy-related signal in the cytoplasm dominates the response time 
      of OxPhos.
FAU - van Beek, J H
AU  - van Beek JH
AD  - Laboratory for Physiology, Institute for Cardiovascular Research, Vrije 
      Universiteit, 1081 BT Amsterdam, The Netherlands. vanbeek@physiol.med.vu.nl
FAU - van Wijhe, M H
AU  - van Wijhe MH
FAU - Eijgelshoven, M H
AU  - Eijgelshoven MH
FAU - Hak, J B
AU  - Hak JB
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Physiol
JT  - The American journal of physiology
JID - 0370511
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Oligomycins)
RN  - 0 (Phosphates)
RN  - 020IUV4N33 (Phosphocreatine)
SB  - IM
MH  - Adaptation, Physiological
MH  - Animals
MH  - Enzyme Inhibitors/pharmacology
MH  - Feedback
MH  - Homeostasis
MH  - In Vitro Techniques
MH  - Mitochondria, Heart/drug effects/metabolism
MH  - Myocardial Contraction
MH  - Myocardium/*metabolism
MH  - Oligomycins/pharmacology
MH  - Oxidative Phosphorylation
MH  - Oxygen Consumption/drug effects
MH  - Phosphates/metabolism
MH  - Phosphocreatine/metabolism
MH  - Rabbits
MH  - Reaction Time
EDAT- 1999/10/12 00:00
MHDA- 1999/10/12 00:01
CRDT- 1999/10/12 00:00
PHST- 1999/10/12 00:00 [pubmed]
PHST- 1999/10/12 00:01 [medline]
PHST- 1999/10/12 00:00 [entrez]
AID - 10.1152/ajpheart.1999.277.4.H1375 [doi]
PST - ppublish
SO  - Am J Physiol. 1999 Oct;277(4):H1375-84. doi: 10.1152/ajpheart.1999.277.4.H1375.