INTERACTION OF CHRONIC CREATINE DEPLETION AND MUSCLE UNLOADING - EFFECTS ON POSTURAL AND LOCOMOTOR MUSCLES

In some rodent skeletal muscles, hindlimb non-weight-bearing activity induces a shift in the expression of myosin heavy chains (MHCs) that f avors the type II isoforms at the expense of type I. Chemically induce d chronic creatine depletion results in isomyosin shifts favoring expr ession of type I MHCs. In this study, creatine depletion was induced s eparately and in combination with non-weightbearing activity to determ ine if the response to lowering this metabolite would counter the MHC transitions expected from non-weight bearing. Creatine depletion was i nduced by feeding rats a diet supplemented with the creatine analogue beta-guanidinopropionic acid (beta-GPA). Female Sprague-Dawley rats we ighing 247 +/- 8 g were randomly assigned to four groups: 1) normal di et control, 2) beta-GPA control (BC), 3) normal diet suspended (NS), a nd 4) beta-GPA suspended (BS). BC and BS animals were fed a diet conta ining the creatine analogue for 68 days. Hindlimb non-weight bearing i n 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% increa se in citrate synthase activity in the soleus (SOL) and a 24% in creas e in the plantaris (PLN). In two postural muscles, the SOL and vastus intermedius (VI), tail suspension resulted in large decreases in the t ype I MHC expression and increases in type IIx and IIb MHCs. In two lo comotor muscles, the PLN and medial gastrocnemius, type I MHC declined and type IIb increased with suspension. Creatine depletion did not pr event the suspension-induced decline in type I MHC in any of these mus cles. The increase in type IIb MHC was either prevented or reduced by creatine depletion before and during suspension in the SOL, VI, and PL N. Creatine depletion alone (BC group) resulted in small increases in type I and IIa MHCs in the two locomotor muscles, but it had no effect on the MHC profile of the postural muscles studied. These results ind icate that, in the adult rodents used in this study, the mechanical si gnal generated by the hindlimb non-weight-bearing state dominated over the metabolic stimulus of creatine depletion with respect to the prim ary adaptation involving a reduction in type I MHC.