Glycolytic buffering affects cardiac bioenergetic signaling and contractile reserve similar to creatine kinase
1 Heart Foundation Research Centre, Griffith University, Gold Coast, Queensland 9726, Australia; and 2 Laboratory for Physiology and 3 Department of Molecular Cell Physiology, Vrije Universiteit, 1081 HV Amsterdam, The Netherlands Submitted 19 August 2002 ; accepted in final form 21 April 2003 Creat...
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Published in | American journal of physiology. Heart and circulatory physiology Vol. 285; no. 2; pp. H883 - H890 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
01.08.2003
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Subjects | |
Online Access | Get full text |
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Summary: | 1 Heart Foundation Research Centre, Griffith
University, Gold Coast, Queensland 9726, Australia; and
2 Laboratory for Physiology and
3 Department of Molecular Cell Physiology, Vrije
Universiteit, 1081 HV Amsterdam, The Netherlands
Submitted 19 August 2002
; accepted in final form 21 April 2003
Creatine kinase (CK) and glycolysis represent important energy-buffering
processes in the cardiac myocyte. Although the role of compartmentalized CK in
energy transfer has been investigated intensely, similar duties for
intracellular glycolysis have not been demonstrated. By measuring the response
time of mitochondrial oxygen consumption to dynamic workload jumps
( t mito ) in isolated rabbit hearts, we studied the effect
of inhibiting energetic systems (CK and/or glycolysis) on transcytosolic
signal transduction that couples cytosolic ATP hydrolysis to activation of
oxidative phosphorylation. Tyrode-perfused hearts were exposed to 15 min of
the following: 1 ) 0.4 mM iodoacetamide (IA; n = 6) to block
CK (CK activity <3% vs. control), 2 ) 0.3 mM iodoacetic acid (IAA;
n = 5) to inhibit glycolysis (GAPDH activity <3% vs. control), or
3 ) vehicle (control, n = 7) at 37°C. Pretreatment
t mito was similar across groups at 4.3 ± 0.3 s
(means ± SE). No change in t mito was observed in
control hearts; however, in IAA- and IA-treated hearts,
t mito decreased by 15 ± 3% and 40 ± 5%,
respectively ( P < 0.05 vs. control), indicating quicker energy
supply-demand signaling in the absence of ADP/ATP buffering by CK or
glycolysis. The faster response times in IAA and IA groups were independent of
the size of the workload jump, and the increase in myocardial oxygen
consumption during workload steps was unaffected by CK or glycolysis blockade.
Contractile function was compromised by IAA and IA treatment versus control,
with contractile reserve (defined as increase in rate-pressure product during
a standard heart rate jump) reduced to 80 ± 8% and 80 ± 10% of
baseline, respectively ( P < 0.05 vs. control), and significant
elevations in end-diastolic pressure, suggesting raised ADP concentration.
These results demonstrate that buffering of phosphate metabolites by
glycolysis in the cytosol contributes appreciably to slower mitochondrial
activation and may enhance contractile efficiency during increased cardiac
workloads. Glycolysis may therefore play a role similar to CK in heart
muscle.
glycolysis; energy transduction; mitochondria; regulation of oxidative phosphorylation
Address for reprint requests and other correspondence: J. H. G. M. van Beek,
Dept. of Molecular Cell Physiology, Faculty of Earth and Life Sciences, Vrije
Universiteit, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands (E-mail:
hans.van.beek{at}falw.vu.nl ). |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0363-6135 1522-1539 |
DOI: | 10.1152/ajpheart.00725.2002 |