Deficiency of α-sarcoglycan differently affects fast- and slow-twitch skeletal muscles

Abstract

Alpha-sarcoglycan (Sgca) is a transmembrane glycoprotein of the dystrophin complex located at skeletal and cardiac muscle sarcolemma. Defects in the alpha-sarcoglycan gene (Sgca) cause the severe human-type 2D limb girdle muscular dystrophy. Because Sgca-null mice develop progressive muscular dystrophy similar to human disorder they are a valuable animal model for investigating the physiopathology of the disorder. In this study, biochemical and functional properties of fast-twitch extensor digitorum longus (EDL) and slow-twitch soleus muscles of the Sgca-null mice were analyzed. EDL muscle of Sgca-null mice showed twitch and tetanic kinetics comparable with those of wild-type controls. In contrast, soleus muscle showed reduction of twitch half-relaxation time, prolongation of tetanic half-relaxation time, and increase of maximal rate of rise of tetanus. EDL muscle of Sgca-null mice demonstrated a marked reduction of specific twitch and tetanic tensions and a higher resistance to fatigue compared with controls, changes that were not evident in dystrophic soleus. Contrary to EDL fibers, soleus muscle fibers of Sgca-null mice distinctively showed right shift of the pCa-tension (pCa is the negative log of Ca2+ concentration) relationships and reduced sensitivity to caffeine of sarcoplasmic reticulum. Both EDL and soleus muscles showed striking changes in myosin heavy-chain (MHC) isoform composition, whereas EDL showed a larger number of hybrid fibers than soleus. In contrast to the EDL, soleus muscle of Sgca-null mice contained a higher number of regenerating fibers and thus higher levels of embryonic MHC. In conclusion, this study revealed profound distinctive biochemical and physiological modifications in fast- and slow-twitch muscles resulting from alpha-sarcoglycan deficiency.

Reduced myofibrillar connectivity and increased Z-disk width in nebulin-deficient skeletal muscle

“…We focused on EDL and soleus muscles because they contain predominately fast and a large number of slow twitch fibers (Danieli-Betto et al, 2005), respectively, allowing us to determine whether there are fiber-type-specific changes in myofibrillar connectivity in the nebulin KO mouse. The ultrastructural sarcomeric organization of WT and nebulin KO muscle is shown in Fig.…”

“…In the absence of nebulin, desmin is unable to bind to these sites on the myofibril and as a result myofibrils differentially translocate when passively stretched. In our work we studied both soleus and EDL muscles, examples of predominately slow-and fastfiber-containing muscles (Danieli-Betto et al, 2005;Girgenrath et al, 2005), respectively. Essentially the same findings were obtained (Fig.…”

Altered Tnnt3 characterizes selective weakness of fast fibers in mice overexpressing FSHD region gene 1 (FRG1)

“…Muscle fibers were chemically skinned as previously described (7,28,38). Briefly, muscles were tied to a wooden stick, stretched to 110 -120% of slack length, and quickly immersed into an ice-cold skinning solution containing 170 mM K-propionate, 2.5 mM Mg-propionate, 2.5 mM Na2K2ATP, 5 mM K2EGTA, 10 mM imidazole buffer, pH 7.0.…”

Sequential stages in the age-dependent gradual formation and accumulation of tubular aggregates in fast twitch muscle fibers: SERCA and calsequestrin involvement

“…Fiber types are mostly classified on the basis of myosin heavy chain isoform expression and myosin ATPase activity. EDL contains ∼70-75% type IIB, ∼10-15% type IIX, ∼8% type IIA, and ∼4% type I (Danieli-Betto et al 2005;Augusto et al 2004;Hughes et al 1999). The reported percentages of the IIX-IIB fibers in EDL are somewhat variable, in part because immunolabeling alone does not always give a clear distinction and in part because the ratios of the two fibers vary in different regions of the muscle and/or in different mouse lines.…”