Effects of Cyclosporine-A on Rat Soleus Muscle Fiber Size and Phenotype

Abstract

Organ transplant patients treated with cyclosporine-A (CsA) often exhibit weight loss and muscle weakness. The cellular target of CsA, calcineurin, has been implicated in maintenance of muscle fiber size and in expression of the type I skeletal muscle phenotype. We hypothesized that CsA treatment would cause fiber atrophy, as well as increase type IIa myosin heavy chain (MHC) content and oxidative enzyme activities in the soleus muscle. Rats were treated with CsA for 21 d (20 mg.kg(-1).d(-1); N = 16) and compared with control rats given olive oil vehicle (Veh; N = 16). Soleus muscles were excised bilaterally. MHC content was determined by gel electrophoresis, oxidative enzyme activities by spectrophotometric methods, and fiber type and size by histochemistry. Lymphocyte count was depressed in CsA rats (P < 0.05), indicating treatment efficacy. Type IIa MHC content was increased in the soleus muscle with CsA (Veh, 10.4 +/- 1.7%; CsA, 15.1 +/- 2.0; P < 0.05) at the expense of type I MHC. Soleus muscle oxidative enzyme activities were also increased with CsA treatment (P < 0.05). Soleus muscle atrophy occurred, reflected by a 22% decrease in fiber cross-sectional area (Veh, 3255 +/- 105 microm(2); CsA, 2533 +/- 125; P < 0.05). These findings indicate that CsA treatment is associated with changes in skeletal muscle fiber size and phenotype. The former may underlie clinical symptoms of transplant patients treated with CsA.