Skeletal Muscle Physiology (Week 1--Homsher) Flashcards
Skeletal muscle fibers
Large diameter (20-100um)
Long (2mm - tens of cm, almost entire length of muscle)
Multi-nucleate
Contain regenerative satellite cells
T-tubules smaller and sarcoplasmic reticulum as much as 7% of cell volume
Much more Ca2+ and calsequestrin in skeletal muscle
Costameres
Sub-sarcolemmal protein assemblies that contain desmin (floppy), dystrophin, gamma-actin
Connect and align Z-disk of myfibrils to each other and to dystroglycans and sarcoglycans (integral membrane proteins)
Integral membrane proteins then bind laminin, fibronectin, collagen in ECM
Costameres and dystrophin link contractile proteins and cytoskeleton to ECM and minimize damage to sarcolemma
Function of costameres
Links and aligns myofibrils with each other and transmits force and displacement occurring in them to ECM and to adjacent muscle cells
Minimizes disruption of phospholipid layer of sarcolemma when muscle length changes significantly during shortening or lengthening
What happens if you have absent or defective dystrophin?
Duchenne Muscular Dystrophy (DMD)
Working muscles damaged when try to undergo concentric and eccentric contraction and make cell membrane leaky to Ca2+ so intracellular proteases activated
Damaged muscle fibers gradually degenerate –> death
Dystrophin located in skeletal and cardiac muscles, brain and lung tissue
Duchenne Muscular Dystrophy (DMD)
Absence of or defect in dystrophin
Disease is due to lack of connection of costameres!
X-linked so only affects males (3/10,000 live births)
Working muscles damaged by concentric and eccentric contractions so cell membrane leaky to Ca2+ and intracellular proteases activated, intracellular creatine kinase appears in blood
Muscle fibers damaged faster than repair –> muscle breakdown or infiltration by macrophages, leukocytes, cytotoxic T cells –> apoptosis –> fat globules or fibrous tissue –> children to wheel chair by age 12, death from respiratory or cardiac disease in teens or 20’s
Becker Dystrophy
Expression of modified or truncated form of dystrophin and produces slowly progressive dystrophy and less severe symptoms than DMD
Myalgias, muscle cramps, reduced exercise tolerance, mild limb girdle weakness
What causes Ca2+ to enter the sarcoplasm in skeletal muscle to trigger contraction?
Depolarization of T-tubules
S4 region (voltage sensing, membrane spanning) of L-type Ca2+ channel (aka DHP receptor) is positively charged and pulls on/opens up Ca2+ pore in RyR in the SR
Ca2+ flows out of SR through RyR
Note: don’t need influx of Ca2+ across sarcolemma to initiate Ca2+ release from SR
Cross bridge mechanism
Same as in cardiac muscle but faster (>2x faster)
Sliding filament mechanism
SKM contracts and relaxes over a wider sarcomere length range (1.6 - >3um)
Force plateau from 2.25 - 2.55um
Calcium regulation of contraction
TnC in SKM contains 2 regulatory Ca2+ binding sites so full activation of SKM requires Ca2+ release at least 2x cardiac muscle
Ca2+ released from SKM SR RyRs by electro-mechanical coupling mechanism (rather than Ca2+-induced Ca2+ release in cardiac muscle)
Active vs. passive force
Active force involves cross bridge interaction, splitting ATP
Passive force is just moving muscle
Can skeletal muscle cells regenerate?
Yes, use satellite cells (stem cells)
Muscle is damaged all the time, so is important to be able to regenerate!
(this is in contrast to cardiac cells)
How do skeletal muscle fibers regenerate?
Fiber injury
Neutrophil invasion, necrosis and autolysis
Macrophage removal of necrotic tissue
Satellite cell mitosis and proliferation
Satellite cell fusion
Fusion to myotube and fusion with fiber stumps
Restoration of original fiber
How many muscle fibers does a single alpha-motor neuron innervate?
Number of muscle cells per motor unit is variable (5-2,000 separate muscle fibers)!
However, each AXON of a neuron only innervates ONE muscle fiber
Does the size of the motor neuron tell you how many muscle fibers it might innervate?
Yes, smaller motor neurons innervate fewer fibers (thus make smaller force) and larger motor neurons innervate more muscle fibers (thus make larger force)
Also means smaller current needed to initiate AP in smaller motor neuron, and larger current needed in larger motor neuron