Combined effects of unloading and Cyclosporin A on myosin heavy chain in slow muscles of rats

Abstract

In skeletal muscle, calcineurin has been associated both in the molecular regulation of fiber-type expression, and in phenotypic responses to altered neuromuscular activity. A decreased calcineurin activity could be involved in the unweighting-induced slow-to-fast myosin transition. This study examines both specific and combined effects of unloading and cyclosporin A (CsA) treatment, a well-known inhibitor of calcineurin, on the distribution of myosin heavy chain (MHC) isoforms in soleus (SOL) and adductor digitorum longus (ADL) muscles of rats. Female rats were randomly assigned to 4 groups (n=8 in each group): weight-bearing or hindlimb-unloaded, treated either by CsA (CsA-WB, CsA-HU) or placebo (WB, HU) daily for 3 weeks. The MHC profile of SOL and ADL was analysed by SDS-PAGE electrophoresis and calcineurin activity estimated by mRNA levels of modulatory calcineurin interacting protein 1 (MCIP-1). A similar slow-to-fast transition was observed in both SOL and ADL of HU, with a de novo expression of MHC-IIX and MHC-IIB. By contrast, in CsA-WB rats a transition limited to MHC-I toward MHC-IIA was observed only in SOL. Unloading and CsA have additional effects on the MHC profile of SOL, whereas in ADL the distribution of MHC was similar in HU and CsA-HU groups. Unloading and CsA decreased MCIP-1 levels in SOL, but have no effect in ADL. These results suggest that a decrease in calcineurin activity cannot fully explain the slow-to-fast transition observed in response to unloading. Support: Service de Santé des Armées