CK inhibition accelerates transcytosolic energy signaling during rapid workload steps in isolated rabbit hearts
Laboratory for Physiology, Institute for Cardiovascular Research, Free University, 1081BT Amsterdam, The Netherlands The effect of graded creatine kinase (CK) inhibition on the response time of mitochondrial O 2 consumption to dynamic workload jumps ( t mito ) was studied in isolated rabbit hearts....
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Published in | American journal of physiology. Heart and circulatory physiology Vol. 276; no. 1; pp. H134 - H140 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
United States
01.01.1999
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Subjects | |
Online Access | Get full text |
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Summary: | Laboratory for Physiology, Institute for Cardiovascular
Research, Free University, 1081BT Amsterdam, The Netherlands
The effect of
graded creatine kinase (CK) inhibition on the response time of
mitochondrial O 2 consumption to
dynamic workload jumps
( t mito ) was
studied in isolated rabbit hearts. Tyrode-perfused hearts
( n = 7/group) were exposed to 15 min
of 0, 0.1, 0.2, or 0.4 mM iodoacetamide (IA) (CK activity = 100, 14, 6, and 3%, respectively). Pretreatment
t mito was similar
across groups at 6.5 ± 0.5 s (mean ± SE). The increase observed
over time in control hearts (33 ± 8%) was progressively reversed
to 16 ± 6, 20 ± 6 ( P < 0.01 vs. control), and 46 ± 6 ( P < 0.01 vs. control) % in the
0.1, 0.2 and 0.4 mM IA groups, respectively. The faster response times occurred without reductions in mitochondrial oxidative capacity (assessed in vitro) or myocardial
O 2 consumption of the whole heart
during workload steps. Isovolumic contractile function assessed as
rate-pressure product (RPP) and contractile reserve (increase in RPP
during heart rate steps) were significantly reduced by IA. We conclude
that CK in the myofibrils and/or cytosol does not speed up
transfer of the energy-related signal to the mitochondria but rather
acts as an energetic buffer, effectively slowing the stimulus between
myofibrils/ion pumps and oxidative phosphorylation. This argues against
the existence of an obligatory creatine phosphate energy shuttle,
because CK is effectively bypassed.
energy transduction; adenosine 5'-diphosphate diffusion; oxygen consumption; contractile reserve |
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ISSN: | 0363-6135 0002-9513 1522-1539 |
DOI: | 10.1152/ajpheart.1999.276.1.H134 |