Muscle Unloading Induces Slow to Fast Transitions in Myofibrillar but not Mitochondrial Properties. Relevance to Skeletal Muscle Abnormalities in Heart Failure

• Published in: Journal of molecular and cellular cardiology Vol. 30; no. 11; pp. 2391 - 2401
• Main Authors: Bigard, A.-X., Boehm, E., Veksler, V., Mateo, P., Anflous, K., Ventura-Clapier, R.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.11.1998
• Subjects: Animals; Calcium sensitivity; Creatine kinase; Creatine Kinase - metabolism; Deconditioning; Electron Transport; Heart Failure - metabolism; Heart Failure - pathology; Heart Failure - physiopathology; Hindlimb suspension; Male; Mitochondria, Heart - metabolism; Mitochondrial respiration; Muscle Fibers, Fast-Twitch - physiology; Muscle Fibers, Slow-Twitch - physiology; Muscle, Skeletal - metabolism; Muscle, Skeletal - physiopathology; Muscle, Skeletal - ultrastructure; Oxygen - metabolism; Oxygen Consumption; Rats; Rats, Wistar; Space life sciences; Mitochondrial respiration; Hindlimb suspension; Calcium sensitivity; Deconditioning; Creatine kinase
• ISSN: 0022-2828; 1095-8584
• DOI: 10.1006/jmcc.1998.0798

Muscle deconditioning is a common observation in patients with congestive heart failure (CHF), chronic obstructive pulmonary disease, neuromuscular diseases or prolonged bed rest. To gain further insight into metabolic and mechanical properties of deconditioned slow-twitch (soleus) or fast-twitch (EDL) skeletal muscles, we induced experimental muscle deconditioning by hindlimb suspension (HS) in rats for 3 weeks. Cardiac muscle was also studied. Besides profound muscle atrophy, increased proportion of fast type II fibers as well as fast myosin isoenzymes, we found decreased calcium sensitivity of Triton X-100 skinned fiber bundles of soleus muscle directed towards the fast muscle phenotype. Glycolytic enzymes such as hexokinase and pyruvate kinase were increased, and the LDH isoenzyme pattern was clearly shifted from an oxidative to an anaerobic profile. Creatine kinase (CK) and myokinase activities were increased in HS soleus towards EDL values. Moreover, the M-CK mRNA level was greatly increased in soleus, with no change in EDL. However, oxygen consumption rate assessedin situin saponin skinned fibers (12.5±0.8 in C and 15.1±0.9μmol O2/min/g dw in HS soleus compared to 7.3±1.3μmol O2/min/g dw in control EDL), as well as mitochondrial CK (mi-CK) and citrate synthase activities, were preserved in HS soleus. Following deconditioning no change in Kmfor ADP of mitochondrial respiration, either in the absence (511±92 in C and 511±111μmin HS soleus compared to 9±4μMin control EDL) or presence of creatine (88±10 in C and 95±16μmin HS soleus compared to 32±9μMin control EDL), was found. The results show that muscle deconditioning induces a biochemical and functional slow to fast phenotype transition in myofibrillar and cytosolic compartments of postural muscle, but not in the mitochondrial compartment, suggesting that these compartments are differently regulated under conditions of decreased activity.