Uncoordinated expression of the main contractile and relaxation proteins in pathological skeletal muscles

Abstract

The sarcoplasmic reticulum Ca2+ ATPase (SERCA) isoforms are normally expressed in coordination with the corresponding myosin heavy chain (MyHC) isoforms in the fibers of skeletal muscle but this coordination is often disrupted in pathological conditions. Here we used three models, the selective denervated soleus (SD), the hindlimb-denervated soleus (HD) and the soleus of streptozotocin-induced diabetic rat (stz-rat) to study such dyscoordinated expressions. SD allowed more passive movement of the soleus, less muscle atrophy, faster transition from slow-to-fast MyHC isoforms and less coordinated expressions of the MyHCs and SERCAs than HD did. Among the investigated isoforms, generally, the expression of the slow-twitch type SERCA2a was the less dependent while the slow-twitch type MyHC1 was the most dependent on innervation. Our study also showed that passive movement is able to ameliorate denervation-induced atrophy, but also accentuates dyscoordinated expression of the corresponding slow and fast MyHC and SERCA isoforms.In stz-rats, the soleus muscle showed peripheral neuropathy and decreased SERCA2a level in type I (slow-oxidative) fibers, till the expression of the corresponding slow MyHC1 did not change compared to the controls. No difference in the mRNA and protein levels of SERCA and MyHC isoforms was found, except that the SERCA2a protein specifically declined in stz-rats compared to the controls. This was enough to disrupt the coordinated expression of SERCA2a and MyHC1 in the diabetic soleus. The results are in line with the observations of other laboratories that regulators of the Ca-homeostasis may adapt faster to type I diabetes than the contractile elements.In conclusion, the slow-to-fast transformations are different in each of the three pathological models. This is in line with previous findings that the expression of MyHC and SERCA isoforms has a multiple control and dyscoordinated in various conditions.