The effect of hypokinesia and hypodynamia on protein turnover and the growth of four skeletal muscles of the rat.

An animal suspension model has been used to simulate the weightlessness experienced during space travel. This procedure results in a reduction in the normal shortening (i.e. hypokinesia) and force generation functions of hind limb muscles (i.e. hypodynamia). The ensuing muscle atrophy was studied over 12 days in different muscle types. Slow muscles (e.g. the soleus) underwent a more pronounced atrophy than intermediate (i.e. gastrocnemius) and fast phasic muscles (e.g. extensor digitorum longus). In all muscle types inactivity resulted in a smaller accumulation of DNA and losses of RNA and protein after 5 days. The latter arose from a decrease in the rate of protein synthesis (measured in vivo) and an increase in protein breakdown. Increased specific activities of cathepsins B and D also supported the view that there is an increased proteolysis after hypokinesia and hypodynamia. When the inactive soleus was simultaneously held in a lengthened (stretched) state the atrophy was prevented through a large increase in the fractional rate of protein synthesis. Protein degradation remained elevated with stretch, thereby slowing the growth of these muscles relative to those in pair-fed, ambulatory controls. The much smaller atrophy of the tibialis anterior and extensor digitorum longus muscles in suspended only limbs represented an underestimate of the true atrophic effects of hypokinesia and hypodynamia. In this model gravity pulls the suspended foot into a plantar flexed position, thereby permanently stretching and protecting such flexor muscles. When this influence of stretch was removed a greater atrophy ensued, mainly due to the loss of the stretch-induced stimulation of protein synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)