Muscle Development, Degeneration and Regeneration Skeletal muscles derived from embryonic somites As development proceeds within somite, single-celled mononucleated muscle fibre pre-cursors appear: myoblasts Myoblasts aggregate into clusters ? form multinucleated cells called myotubules Further increase in length occurs as more myoblasts fuse to myotube ends Primary myotubes and some other less differentiated cells separate into clusters surrounded by a sheath called the basement membrane More myoblasts aggregate beneath BM using primary tubule as a scaffold Blunt trauma Surgery Ischaemia Myotoxic anaesthetics (local) Eccentric contraction Myoglobin Creatine kinase (MM-CK isoform) o Specific to skeletal muscle and is localised at contractile proteins Lactate dehydrogenase (LDH) (skeletal muscle specific isoenzyme) Metabolic Mechanical o Trauma Eccentric contraction Pain/tenderness 12-24 hours after eccentric exercise Intramuscular soluble protein release peaks 2-4 days after eccentric contraction Destruction of muscle infiltrated by mononucleocytes 6-10 days later Satellite cell activation ? 2-3 weeks to restore function Variable muscle diameter Some fibres don’t mature fully and retain internal nuclei Groups of fibres enclosed in fibrous sheath Incomplete fusion ? branching and splitting Contraction times, max shortening velocity, fibre length, cross sectional area return to normal Restoration of muscle mass, peak tetanic tension and muscle endurance can lag behind Note: in all types of damage, intracellular concentration of Ca is the trigger of necrosis Defects in proteins linking cytoskeleton protein dystrophin to ECM protein laminin-2 ( merosin ) ? Important proteins: Dystrophin, dystroglycan complex (associated with laminin-2) and sarcoglycan complex Dystrophin anchors actin to sarcolemma