Isoform-Specific Na,K-ATPase Alterations Precede Disuse-Induced Atrophy of Rat Soleus Muscle

This study examines the isoform-specific effects of short-term hindlimb suspension (HS) on the Na,K-ATPase in rat soleus muscle. Rats were exposed to 24-72 h of HS and we analyzed the consequences on soleus muscle mass and contractile parameters; excitability and the resting membrane potential (RMP) of muscle fibers; the electrogenic activity, protein, and mRNA content of the alpha 1 and alpha 2 Na,K-ATPase; the functional activity and plasma membrane localization of the alpha 2 Na,K-ATPase. Our results indicate that 24-72 h of HS specifically decreases the electrogenic activity of the Na, K-ATPase alpha 2 isozyme and the RMP of soleus muscle fibers. This decrease occurs prior to muscle atrophy or any change in contractile parameters. The alpha 2 mRNA and protein content increased after 24 h of HS and returned to initial levels at 72 h; however, even the increased content was not able to restore alpha 2 enzyme activity in the disused soleus muscle. There was no change in the membrane localization of alpha 2 Na, K-ATPase. The alpha 1 Na, K-ATPase electrogenic activity, protein and mRNA content did not change. Our findings suggest that skeletal muscle use is absolutely required for alpha 2 Na, K-ATPase transport activity and provide the first evidence that Na, K-ATPase alterations precede HS-induced muscle atrophy.