METABOLIC RESPONSES OF SKELETAL MUSCLE TO HYPOKINESIA/HYPODYNAMIA (ATROPHY, AMINO ACID, PROTEIN TURNOVER).

Abstract

The metabolic response to muscle unloading and disuse was studied in rats subjected for six days to tail-cast suspension which leads to non-weight bearing hindlimbs, while the forelimbs are utilized for mobility. Under these conditions the soleus muscle atrophied, growth of the gastrocnemius and plantaris muscles declined, and the extensor digitorum longus and tibialis anterior muscles grew normally. Differences in muscle weight and protein content were associated with slower protein synthesis, particularly in the sarcoplasmic fraction, and faster protein degradation. Atrophy was accentuated by the administration of glucocorticoids to adrenalectomized rats causing a further reduction in protein synthesis. The effects of disuse and glucocorticoids were additive. Amino acid metabolism is altered in disuse of the soleus muscle as demonstrated by higher concentrations of tyrosine and glutamate and lower concentrations of glutamine, aspartate and asparagine. The lower glutamine concentration is the result of slower de novo synthesis despite higher glutamine synthetase activity, the result of glucocorticoid action. Slower glutamine synthesis was due to a lack of free ammonia for its synthesis, probably due to slower flux through AMP deaminase as a result of decreased muscle use and ATP utilization. Alanine production by the atrophied soleus muscles was higher and glutamate and aspartate utilization lower than by muscles from weight bearing controls. Branched chain amino acid degradation is faster in both the soleus and extensor digitorum longus muscles of suspended rats; a difference partially mediated by glucocorticoids. The resistance of amino acid uptake to insulin in these muscles was abolished in adrenalectomy. Passive stretch of the non-weight bearing soleus muscle, by immobilization in dorsiflexion, prevented the metabolic changes associated with hindlimb suspension while plantar flexion had no effect on the atrophy. Muscles subjected to hypokinesia/hypodynamia demonstrated a loss of muscle protein due to slower protein synthesis and faster degradation. The increased availability of free amino acids from protein coupled to differences in hormone responsiveness and slower utilization of energy stores results in a substantial shift in the metabolic equilibrium of the muscle cell, particularly with regard to amino acid interconversions.