Interaction of chronic creatine depletion and muscle unloading: effects on postural locomotor muscles.
In some rodent skeletal muscles, hindlimb non-weight-bearing activity induces a shift in the expression of myosin heavy chains (MHCs) that favors the type II isoforms at the expense of type I. Chemically induced chronic creatine depletion results in isomyosin shifts favoring expression of type I MHCs. In this study, creatine depletion was induced separately and in combination with non-weight-bearing activity to determine if the response to lowering this metabolite would counter the MHC transitions expected from non-weight bearing. Creatine depletion was induced by feeding rats a diet supplemented with the creatine analogue beta-guanidinopropionic acid (beta-GPA). Female Sprague-Dawley rats weighing 247 +/- 8 g were randomly assigned to four groups: 1) normal diet control, 2) beta-GPA control (BC), 3) normal diet suspended (NS), and 4) beta-GPA suspended (BS). BC and BS animals were fed a diet containing the creatine analogue for 68 days. Hindlimb non-weight bearing in BS and NS animals was accomplished by tail suspension for the final 30 days of this period. beta-GPA feeding lowered the creatine content of muscles sampled by 65%. Creatine depletion resulted in a 16% increase in citrate synthase activity in the soleus (SOL) and a 24% increase in the plantaris (PLN). In two postural muscles, the SOL and vastus intermedius (VI), tail suspension resulted in large decreases in the type I MHC expression and increases in type IIx and IIb MHCs. In two locomotor muscles, the PLN and medial gastrocnemius, type I MHC declined and type IIb increased with suspension.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Physiology and Biophysics, University of California, Irvine 92717.
G R
GR
Adams
F
F
Haddad
K M
KM
Baldwin
D000818:Animals; D001483:Base Sequence; D002950:Citrate (si)-Synthase / Q000378:metabolism; D003401:Creatine / Q000172:deficiency*; D005260:Female; D006146:Guanidines / Q000494:pharmacology; D006614:Hindlimb; D008969:Molecular Sequence Data; D018485:Muscle Fibers, Skeletal / Q000502:physiology; D009124:Muscle Proteins / Q000096:biosynthesis / Q000737:chemistry; D018482:Muscle, Skeletal / Q000378:metabolism*; D009218:Myosins / Q000096:biosynthesis* / Q000235:genetics; D010641:Phenotype; D011422:Propionates / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D016474:Weight-Bearing
D006146:Guanidines; D009124:Muscle Proteins; D011422:Propionates; D012333:RNA, Messenger; D002950:Citrate (si)-Synthase; D009218:Myosins; D003401:Creatine; C005775:guanidinopropionic acid