Functional characteristics of skeletal muscle in alfa-sarcoglycan-deficient mouse

α-Sarcoglycan (aSG) is a transmembrane glycoprotein, component of the dystrophin complex, and its absence produces in man a severe form of limb-girdle muscular dystrophy. This study was undertaken in a α-sarcoglycan-deficient (aSG-null) mouse to evaluate whether the absence of the protein from sarcolemma affects the functional properties of slow- (soleus) and fast-twitch (EDL) skeletal muscles. At three months of age, the majority of fibers from soleus and EDL display centrally located nuclei. Muscle mass of both soleus and EDL is significantly higher than controls. However, hypertrophic EDL muscle shows peak tetanic tension (P0) values lower than control levels and the resultant relativeP0 is significantly reduced. At variance, hypertrophic soleus muscle had values comparable to controls with a resultant specific force not different from control. The initial maximal velocity of rise of tetanic tension is reduced in EDL and unchanged in soleus. The force-frequency relationship is only slightly changed in soleus, whereas it is highly shifted to the left in EDL, an indication of slowing (it should be associated to the increase of CT, however not found), similarly to what was reported in the mdx mice. Fatigability is also significantly changes in EDL muscle, whereas no modifications occur in soleus. In fact, EDL presents an initial tension potentiation not seen in control. At variance, SDH analysis shows that the oxidative capacity of EDL and soleus muscles is comparable to control. Fiber type composition, as determined by immunofluorescence and SDS-PAGE analysis of MHC isoforms expression, demonstrates in 3-month old aSG-null EDL the rise of type 2X-2B at detriment of type 2B fibers, the significant reduction of type 2A fibers and, similarly to control, very rare type 1 fibers. At variance, in soleus muscle the main difference is the significant expression of embryonic MHC, not detected in the EDL, and the rise of type 2X MHC. The expression level of sarcoplasmic reticulum Ca2+-pump (SERCA) isoforms was also investigated. While EDL muscle expressed the SERCA1 isoform only both in control and dystrophic muscle, in soleus both isoforms, SERCA1 and SERCA2 were present. The study extended the analysis in single fibers, identified by the expressed MHC isoforms. First, several dystrophic fibers show the contemporary presence of hybrid myosins, a picture noted also in few control fibers. Ca2+ sensitivity of myofibrillar proteins, determined by pCa-tension relationships, was apparently not different in EDL and soleus dystrophic fibers in respect to control. Caffeine sensitivity of sarcoplasmic reticulum Ca2+ release caffeine was reduced in EDL (from 3.85 to 2.96) and significantly increased in soleus (from 2.50 to 4.29). Several studies suggest that the dystrophin complex is critical for structural integrity of the myofiber plasma membrane. Muscle physiology studies show that changes in muscle structure and function, downstream of the specific, primary biochemical deficiency, alter muscle contractile properties. In the αSG-null mouse, fast-twitch muscles appear to be significantly more affected than slow-twitch muscles.