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

Am J Physiol Regul Integr Comp Physiol. 2005 Nov;289(5):R1328-37. doi: 10.1152/ajpregu.00673.2004. Epub 2005 Jul 7.


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.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Caffeine / pharmacology
  • Calcium / metabolism
  • Calcium / pharmacology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Muscle Contraction / physiology
  • Muscle Fibers, Fast-Twitch / drug effects
  • Muscle Fibers, Fast-Twitch / physiology*
  • Muscle Fibers, Slow-Twitch / drug effects
  • Muscle Fibers, Slow-Twitch / physiology*
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / physiology*
  • Myosin Heavy Chains / genetics
  • Myosin Heavy Chains / metabolism
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Sarcoglycans / deficiency*
  • Sarcoglycans / genetics
  • Sarcoplasmic Reticulum / drug effects
  • Sarcoplasmic Reticulum / metabolism*


  • Protein Isoforms
  • Sarcoglycans
  • Caffeine
  • Myosin Heavy Chains
  • Calcium