Skeletal muscle Flashcards
What cell types make up skeletal muscle?
- skeletal myocytes
- endothelial cells of the vascular system which nourishes it
- connective tissue fibroblasts
Describe the hierarchical structure of skeletal muscle (largest to smallest). Where are the nuclei in this structure?
gross anatomical muscle (cm) > fascicles (mm) > skeletal myocytes (aka “fibers”: 10-100 um) > myofibrils (~1 um) > myofilaments (nm)
**hundreds of nuclei at the myocyte periphery
Describe the connective tissue of skeletal muscle
- entire muscle is surrounded by deep fascia aka epimysium
- each fascicle is surrounded by perimysium (continous with CT at myotendon junction)
- each skeletal myocyte within a fascicle is surrounded by endomysium (continuous with the basal lamina/basement membrane)
Describe the striated structure of a myocyte. What is a sarcomere?
Myocytes contain myo_fibrils;_
- light bands (I-bands)
- bisected by a Z-line (contains the protein alpha-actinin)
- dark bands (A-bands)
- H-zone down the middle, bisected by M-line (contains MM-CK)
**sarcomere= area between successive Z-lines (fundamental unit of striated muscle contraction)
Describe myofibril structure
**myofibrils contain myofilaments
- Thick= A bands only
- myosin
- note; A bands are dark because they contain both thick and thin filaments
- Thin= I bands and A bands
- actin, 3 troponins, tropomyosin
- note; I bands are light because they ONLY contain thin filaments
What is a triad?
At the A-I junction, two SR membranes plus one T-tubule membrane
Describe the excitation phase of muscle contraction
**how striated muscle contracts;
- neuron is activated, Ca++ enters
- synaptic vesicles in the nerve terminal fuse with pre-synaptic membrane and empty their contents
- acetylcholine (ACh) enters intercellular space (cleft) -> 2 ACh molecules bind to each acetylcholine receptor (AChR)
- nicotinic AChRs function as Na+ ion channels on the myocyte’s post-synaptic membrane (acetylcholinesterase modulates the extent of synaptic transmission)
- entry of Na+ ions into the myocyte, igniting the action potential -> wave of depolarization runs down the sarcolemma and dives into the T-tubules
- T tubules contain the Ca++ channel protein Cav1.1 (aka DHP receptor)
- Cav1.1 binds a ryanodine (RyR) receptor on the membrane of the SR, causing the SR to release its stored Ca++
What are neuromuscular blockers?
- non-depolarizing agents (curariform drugs), which bind-up ACh ligand
- depolarizing agents such as succinylcholine, which overstimulate the AChR, causing it to become non-reponsive
**have no CNS activity
Describe the contraction phase of muscle contraction
- Ca++ released by the SR binds troponin-C (thin filament protein)
- causes tropomyosin to move, uncovering myosin-binding-sites on actin (thin filament)
- as the thick filament rotates, the myosin head (activated by ATP hydrolysis) binds actin
- myosin head flexes, thin filament move into the A-band
- sarcomere shortens (length of A band unchanged, I band shortens)
How does Striated Muscle Relax?
- Ca++ ion-channel pump (SERCA) in the SR membrane pumps Ca++ back into the SR
- decreased Ca++ -> fresh ATP binds the myosin head -> actin and myosin disssociate -> myocyte relaxes
Describe malignant hyperthermia
- mutation in CACNA1 (gene encoding Cav1.1) or Ryr1 (gene encoding ryanodine receptor) dysregulates Ca++ transport
- leads to sustained contraction -> increased body temp
- fix with dantrolene, a muscle relaxant that blocks Ca++ release from the SR by inhibiting the ryanodine receptor
**contrast rigor mortis= the absence of fresh ATP prevents acto-myosin dissociation, preventing relaxation and resulting in “stiffening“
What is the ratio of thick:thin filaments within a myocyte?
within each myofibril there are six thin filaments surrounding each thick filament
(also parts of the SR membrane system surround each myofibril)
How is energy stored for muscle contraction?
- Skeletal muscle stores energy as ATP, creatine phosphate, glycogen, and fatty acids.
- sprinters use glycogen
- marathoners utilize fatty acids
What are the types of muscle fibers?
- Type I fibers “slow twitch” fibers
- red (enriched in mitochondria and myoglobin)
- for fatty acid oxidation and oxidative metabolism to support relatively continuous contraction
- __Type II fibers “fast twitch fibers”
- white (less myoglobin); glycolytic or mixed oxidative/glycolytic
- modified for rapid, discontinuous contraction
- sub-classified as Type IIA, IIB and IIC, based on biochemical composition
From what type of cell does skeletal muscle regenerate? What signals regulate the process?
- via Resident Adult Stem Cells (mononuclear, residing between the sarcolemma and the basal lamina of the skeletal myocyte; their niche)
- also called satellite cells/skeletal myoblasts
- normally arrested in Go phase (thanks to myostatin) of the cell-cycle (re-enter cycle when basal lamina is damaged and releases growth factors)
Describe the steps of skeletal muscle regeneration
- Resident Adult Stem Cells are stimulated by growth factors to leave the Go phase and begin division/expansion
- after expansion, the cells irreversibly withdraw from the cell-cycle and fuse together, forming multinuclear muscle cells termed myotubes
- myotubes undergo robust muscle differentiation and can regenerate entire muscles
