METABOLIC ADAPTATION OF SKELETAL-MUSCLES TO GRAVITATIONAL UNLOADING

Responses of high-energy phosphates and metabolic properties to hindli mb suspension were studied in adult rats. The relative content of phos phocreatine (PCr) in the calf muscles was significantly higher in rats suspended for 10 days than in age-matched cage controls. The Pi/PCr r atio, where Pi is inorganic phosphate, in suspended muscles was less t han controls. The absolute weights of soleus and medial gastrocnemius (MG) were approximately 40% less than controls. Although the % fiber d istribution in MG was unchanged, the % slow fibers decreased and the % fibers which were classified as both slow and fast was increased in s oleus. The activities (per unit weight or protein) of succinate dehydr ogenase and lactate dehydrogenase in soleus were unchanged but those o f cytochrome oxidase, beta-hydroxyacyl CoA dehydrogenase, and citrate synthase were decreased following unloading. None of these enzyme acti vities in MG changed. However, the total levels of all enzymes in whol e muscles decreased by suspension. It is suggested that shift of slow muscle toward fast type by unloading is associated with a decrease in mitochondrial biogenesis. Further, gravitational unloading affected th e levels of muscle proteins differently even in the same mitochondrial enzymes. Unloading-related atrophy is prominent in red muscle or slow -twitch fiber1,2. Such atrophy is accompanied by a shift of contractil e properties toward fast-twitch type 2-9. Further, inhibition of mitoc hondrial metabolism in these muscles is also reported by some studies 10-14 suggesting a lowered mitochondrial biogenesis, although results from some studies do not necessarily agree1,7,15. However, the precise mechanism responsible for such alterations of muscle properties in re sponse to gravitational unloading is unclear. On the contrary, mitocho ndrial biogenesis, suggested by mitochondrial enzyme activities and/or mass, is stimulated in muscles with depleted high-energy phosphates b y cold exposure16 and/or by feeding creatine analogue beta-guanidinopr opionic acid17-19. Tension production may be inhibited in unloaded ant igravity muscles20, although the muscular activity detected by electro myography is not necessarily decreased21. Thus, the contents of high-e nergy phosphates or turnover rate of adenosine triphosphate (ATP), whi ch then affect the mitochondrial energy metabolism, may be altered. Th erefore, the responses of high-energy phosphates and metabolic propert ies of rat hindlimb muscles to gravitational unloading were investigat ed.