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Updated: Oct 1, 2026
Measurement of Oxygen Consumption Rate in Acute Striatal Slices from Adult Mice
Published on: June 8, 2022
Activation time of myocardial oxidative phosphorylation in creatine kinase and adenylate kinase knockout mice
Lori A Gustafson1, Johannes H G M Van Beek
1Laboratory for Physiology, Institute for Cardiovascular Research, Vrije Universiteit, 1081 BT Amsterdam, The Netherlands. hvanbeek@bio.vu.nl
Abstract:
Our goal was to determine whether mice genetically altered to lack either creatine kinase (M/MtCK(-/-)) or adenylate kinase (AK(-/-)) show altered properties in the dynamic regulation of myocardial oxygen consumption (MVO(2)). We measured contractile function, oxygen consumption, and the mean response time of oxygen consumption to a step increase in heart rate [i.e., mitochondrial response time (t(mito))] in isolated Langendorff-perfused hearts from wild-type (n = 6), M/MtCK(-/-) (n = 6), and AK(-/-) (n = 4) mice. Left ventricular developed pressure was higher in M/MtCK(-/-) hearts (88.2 +/- 6.8 mmHg) and lower in AK(-/-) hearts (46.7 +/- 9.4 mmHg) compared with wild-type hearts (60.7 +/- 10.1 mmHg) at the basal pacing rate. Developed pressure fell slightly when heart rate was increased in all three groups. Basal MVO(2) at 300 beats/min was 19.1 +/- 2.4, 19.4 +/- 1.5, and 16.3 +/- 1.9 micromol x min(-1) x g dry wt(-1) for M/MtCK(-/-), AK(-/-), and wild type, respectively, which increased to 25.5 +/- 3.7, 25.4 +/- 2.6, and 22.0 +/- 2.6 micromol. min(-1) x g(-1), when heart rate was increased to 400 beats/min. The t(mito) was significantly faster in M/MtCK(-/-) hearts: 3.0 +/- 0.3 versus 7.3 +/- 0.6 and 8.0 +/- 0.4 s for M/MtCK(-/-), AK(-/-), and wild-type hearts, respectively. Our results demonstrate that MVO(2) of M/MtCK(-/-) hearts adapts more quickly to an increase in heart rate and thereby support the hypothesis that creatine kinase acts as an energy buffer in the cytosol, which delays the energy-related signal between sites of ATP hydrolysis and mitochondria.
Insights
Mice lacking creatine kinase (M/MtCK(-/-)) showed faster myocardial oxygen consumption (MVO(2)) adaptation to increased heart rate. This supports creatine kinase acting as a cytosolic energy buffer, delaying signals between ATP use and mitochondria.
Area of Science:
- Physiology
- Biochemistry
- Cardiovascular Research
Background:
- Mitochondrial energy buffering is crucial for dynamic regulation of myocardial oxygen consumption (MVO(2)).
- Creatine kinase (CK) and adenylate kinase (AK) are key enzymes in cellular energy metabolism.
- The role of CK and AK in the dynamic regulation of cardiac energy metabolism remains incompletely understood.
Purpose of the Study:
- To investigate the impact of genetic ablation of M/MtCK or AK on the dynamic regulation of MVO(2) in mouse hearts.
- To determine if CK or AK deficiency alters the response time of mitochondrial oxygen consumption to increased cardiac workload.
Main Methods:
- Isolated Langendorff-perfused hearts from wild-type, M/MtCK(-/-), and AK(-/-) mice were used.
- Contractile function, MVO(2), and mitochondrial response time (t(mito)) were measured.
- MVO(2) response to a step increase in heart rate was analyzed.
Main Results:
- M/MtCK(-/-) hearts exhibited higher basal left ventricular developed pressure compared to wild-type and AK(-/-) hearts.
- The mitochondrial response time (t(mito)) was significantly faster in M/MtCK(-/-) hearts (3.0 s) compared to wild-type (8.0 s) and AK(-/-) (7.3 s) hearts.
- MVO(2) in M/MtCK(-/-) hearts adapted more rapidly to increased heart rate.
Conclusions:
- Genetic deletion of M/MtCK accelerates the dynamic regulation of MVO(2) in the heart.
- These findings support the hypothesis that creatine kinase functions as a cytosolic energy buffer.
- CK buffering delays the energy-related signal transmission between ATP hydrolysis sites and mitochondria.
