Effects of testosterone suppression, hindlimb immobilization, and recovery on [3H]ouabain binding site content and Na+, K+-ATPase isoforms in rat soleus muscle

We investigated the effects of testosterone suppression, hindlimb immobilization, and recovery on skeletal muscle Na,K-ATPase (NKA), measured via [3H]ouabain binding site content (OB) and NKA isoform abundances (=1 3, =1 2). Male rats underwent castration or sham surgery plus 7 days of rest, 10 days of unilateral immobilization (cast), and 14 days of recovery, with soleus muscles obtained at each time from cast and noncast legs. Testosterone reduction did not modify OB or NKA isoforms in nonimmobilized control muscles. With sham surgery, OB was lower after immobilization in the cast leg than in both the noncast leg (α26%, P = 0.023) and the nonimmobilized control (α34%, P = 0.001), but OB subsequently recovered. With castration, OB was lower after immobilization in the cast leg than in the nonimmobilized control (α34%, P = 0.001), and remained depressed at recovery (α34%, P = 0.001). NKA isoforms did not differ after immobilization or recovery in the sham group. After castration, =2 in the cast leg was ~60% lower than in the noncast leg (P = 0.004) and nonimmobilized control (P = 0.004) and after recovery remained lower than the nonimmobilized control (α42%, P = 0.039). After immobilization, =1 was lower in the cast than the noncast leg (α26%, P = 0.018), with =2 lower in the cast leg than in the noncast leg (α71%, P = 0.004) and nonimmobilized control (α65%, P = 0.012). No differences existed for =1 or =3. Thus, both OB and =2 decreased after immobilization and recovery in the castration group, with =2, =1, and =2 isoform abundances decreased with immobilization compared with the sham group. Therefore, testosterone suppression in rats impaired restoration of immobilization-induced lowered number of functional NKA and =2 isoforms in soleus muscle. NEW & NOTEWORTHY: The Na,K-ATPase (NKA) is vital in muscle excitability and function. In rats, immobilization depressed soleus muscle NKA, with declines in [3H]ouabain binding, which was restored after 14 days recovery. After testosterone suppression by castration, immobilization depressed [3H]ouabain binding, depressed =2, =1, and =2 isoforms, and abolished subsequent recovery in [3H]ouabain binding and =2 isoforms. This may have implications for functional recovery for inactive men with lowered testosterone levels, such as in prostate cancer or aging.