Muscle creatine kinase-deficient mice. I. Alterations in myofibrillar function.
The regulation of contractile activity in mice bearing a null mutation of the M-isoform of creatine kinase gene, has been investigated in tissue extracts and Triton X-100-treated preparations of ventricular, soleus, and gastrocnemius muscles of control and transgenic mice. Skinned fiber experiments did not evidence any statistical difference in the maximal force or the calcium sensitivity of either muscle type. Rigor tension development at a low MgATP concentration was greatly influenced by phosphocreatine in control but not in transgenic mice as should be expected. In calcium-activated ventricular preparations, although the force developed by each cross-bridge was the same in control and transgenic animals, the rate constant of tension changes appeared to be markedly slowed in transgenic animals. As the ventricular isomyosin pattern was not altered, we suggested that, in transgenic animals, cross-bridge cycling was hindered by a local decrease in the MgATP to MgADP ratio, due to lack of a local MgATP regenerating system. Myokinase activity was not significantly changed while activities of pyruvate kinase or glyceraldehyde-3-phosphate dehydrogenase were found to be increased in transgenic animals. These results show that no fundamental remodelling occurs in myofibrils of transgenic animals but that important adaptations modify the bioenergetic pathways including glycolytic metabolism.
Ventura-Clapier
R
R
Laboratoire de Cardiologie Cellulaire et Moléculaire, CJF INSERM 92-11, Faculté de Pharmacie, Université Paris-Sud, Châtenay-Malabry, France.
Kuznetsov
A V
AV
d'Albis
A
A
van Deursen
J
J
Wieringa
B
B
Veksler
V I
VI
D000222:Adaptation, Physiological; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D003402:Creatine Kinase / Q000172:deficiency* / Q000235:genetics; D004195:Disease Models, Animal; D004734:Energy Metabolism; D005260:Female; D006019:Glycolysis; D066298:In Vitro Techniques; D007527:Isoenzymes; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009119:Muscle Contraction / Q000235:genetics / Q000502:physiology; D018482:Muscle, Skeletal / Q000201:enzymology*; D009200:Myocardial Contraction / Q000235:genetics / Q000502:physiology; D009206:Myocardium / Q000201:enzymology*; D009210:Myofibrils / Q000201:enzymology / Q000235:genetics / Q000502:physiology*; D009218:Myosins / Q000378:metabolism
D007527:Isoenzymes; D000255:Adenosine Triphosphate; D003402:Creatine Kinase; D009218:Myosins