Activation time of myocardial oxidative phosphorylation in creatine kinase and adenylate kinase knockout mice

• Published in: American journal of physiology. Heart and circulatory physiology Vol. 282; no. 6; pp. H2259 - H2264
• Main Authors: Gustafson, Lori A, Van Beek, Johannes H. G. M
• Format: Journal Article
• Language: English
• Published: United States 01.06.2002
• Subjects: Adenosine Triphosphate - metabolism; Adenylate Kinase - deficiency; Adenylate Kinase - physiology; Animals; Creatine Kinase - deficiency; Creatine Kinase - physiology; Female; Heart Rate; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mitochondria, Heart - metabolism; Myocardium - metabolism; Myocardium - ultrastructure; Oxidative Phosphorylation; Oxygen Consumption; Time Factors; Ventricular Function, Left; Ventricular Pressure
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.00264.2001

Laboratory for Physiology, Institute for Cardiovascular Research, Vrije Universiteit, 1081 BT Amsterdam, The Netherlands 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 (M O 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 M O 2 at 300 beats/min was 19.1 ± 2.4, 19.4 ± 1.5, and 16.3 ±   1.9 µmol · min 1 · 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 µmol · min 1 · 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 M O 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. oxygen consumption; mitochondria; metabolic wave