Skeletal Muscle Flashcards
Organization of skeletal muscle
- each fiber is a long multinucleated cell (formed by fusion of myoblasts during development)
- fibers vary in size
- each fiber contains myofibril for contraction
Skeletal muscle general characteristics
- striated
- multinucleated
- attaches to bone
- somatic NS
- isolated from neighboring cells
Myofibrils
thin rod-like structures used for contraction
composed of many sarcomeres end to end
-organelles, many per muscle fiber (cell)
Muscle fibers attach to plasma membrane via:
adherens junctions which attach to tendons via the basal lamina
Fascicles
bundles of muscle fibers visible to the naked eye
epimysium
fascia (connective tissue) that surrounds the muscle and separates it from its neighbors
endomysium
surrounds each muscle fiber
very thin septa
separates fibers electrically
constitutes the BM and some CT
perimysium
medium thickness
surrounds the fascicles
Sarcomere
structural and functional unit of striated muscle contraction
contains overlapping thin (actin) and thick (myosin) filaments
the barbed ends of these filaments are anchored in the z-disk
the myosin (thick) binds to actin (thin)
M Line
central link between bipolar myosin filaments
Z disk
crosslinks the thin filaments
polarity on one end of the z line is the same
Z disk (line) contains
alpha actinin
Cap Z
proteins
What happens in a sarcomere during muscle contraction
thin filaments slide past the thick filaments
distance between z disks increases
cyclic interaction of myosin and actin powers contraction
I Band
no thick filament overlapping the thin
space between the z disks
Tension depends on
the number of myosin heads overlapped by thin filaments
-FORCE
Myosin
from a superfamily (39 genes in humans)
Myosin II is the molecular motor for muscle contraction
polymerizes at tails to form bipolar filaments
Myosin II structure
total 6 polypeptide chains: composed of 2 heavy chains, 4 light
each heavy chain has a regulatory light chain and an essential light chain
3 structural domains
1) motor
2) subfragment (allows swing)
3) Light meromyosin (LMM)
Myosin motor structure
regulatory domains on the heavy chain are alpha helices that extend from the motor domain and at as lever arm
Actin
second most abundant protein on earth
DNA sequence is highly conserved
monomeric actin (g-actin) polymerizes to form filaments (f-actin)
G Actin
binds ADP/ATP
hydrolysis is slow
G Actin polymerization
upon polymerization ATP rapidly hydrolyzed
associate/disassociate only at the ends
the filament is POLARIZED
pointed end - minus end
barbed end - plus end (anchored in z-disk)
Myosin/Actin binding
- tight in the absence of ATP (rigor)
- weakened by ATP
- actin accelerates myosin ATPase
- myosin heads bind actin at an angle at barbed end, moves towards the barbed ends via powerstroke
Energy for motility
1) myosin binding to ATP releases actin
2) myosin ATP hydrolysis, ADP/P stay tightly bound and the myosin filament cocks (reverse power stroke)
3) myosin reattaches to actin
4) P leaves and myosin returns to uncocked state (force generating power stroke)
Myosin ATPase
activity increased by actin
tropomodulin
-capping protein regulates actin polymerization/depolymerization at the pointed ends
CapZ
capping protein that regulates actin polymerization/depolymerization at the barbed end
Titin
giant protein that forms elastic connections between z disks and myosin
Z disks connect to the plasma membrane via
intermediate filaments
What stabilizes the plasma membrane of skeleton muscle?
dystrophin and proteins
issues in these can cause muscular dystrophy
Innervation of muscle fiber
at single motor end plate
each fiber has its own, separate innervation
Excitation/contraction coupling
- contraction due to acetyl choline release at end plate causing depolarization of surface membrane
- depolarization spreads via action potential
- calcium acts as second messenger to allow the disinhibition of the actin/myosin system and causes contraction
Motor Unit
single neuron innervates many muscle fibers through branching (all the same type)
skeletal muscles contain numerous motor units
fibers of a motor unit are dispersed and intermingle with other fibers
small motor units reach firing threshold easier
activation of one motor unit
weak but distributed contraction
activation of multiple motor units
stronger contraction
Twitch
mechanical response due to a single action potential
briefest normal contraction of a skeletal muscle
Tetanus
fused twitches
Skeletal muscle action potential has a positive after twitch because:
- t tubular and surface membranes are electronically coupled
- action potential in the t tubular membrane occurs slightly after
Depolarization of plasma membrane (sarcolemma) causes
calcium release from sarcoplasmic reticulum
Transverse tubules
- invaginations of the plasma membrane
- membrane is continuous with plasma membrane, lumen with the extracellular space
- between the cisterna of the sarcoplasmic reticulum (feet where Ca released from SARCOPLASMIC RETICULUM NOT ECM)
Mechanisms of calcium removal from the cytoplasm
Out to Extracellular:
- Ca/H pump (ATP linked)
- Na/Ca pump
Back to SR:
- H/Ca pump (ATP linked)
- bound to calcireticulin and calcisequestrin
Muscle can be found in three states:
- relaxed
- contracted
- rigor
Relaxation
- regulatory proteins prevent actin/myosin interaction
- few heads are bound to actin
- sarcomere can be stretched passively
Contraction state
- muscle activated by calcium release
- thousands of sarcomeres shorten in series causing the muscle to shorten
- ATP is hydrolyzed and force is produced
Rigor State
- ATP is depleted
- all myosin heads are bound to actin
- strong actin/myosin interaction prevents stretching
Nerve stimulation determines the contractile force in two ways:
1) the NUMBER of motor units determines how many muscle cells produce force
2) the RATE of stimulation adjusts the force produced by active cells
Muscle contraction activated by
calcium
Muscle contraction is regulated by
thin filaments - tropomyosin and troponin
Tropomyosin
- calcium sensitive regulatory protein
- 2 alpha helice polypeptides
- at low calcium (relaxation) it is bound to actin and blocks myosin
Troponin
- 3 proteins
- TN-C binds calcium
- TN-I inhibits actin/myosin interaction
- TN-T binds tropomyosin
- When bound to calcium it causes the release of tropomyosin
Length-tension relation
force production is proportional to the number of site that crossbridges (actin/myosin interactions) can form
Total tension
active + passive
Active tension
due to contraction (actin and myosin)
Passive tension
due to other elastic elements parallel to contractile elements
-example: titin
Force production
- depends on the number of myosin molecules/area and the fraction of their ATPase cycle
- proportional to fiber diameter (fibers in series have the same tension as a single fiber)
- maximum force depends on the number of fibers in PARALLEL
- Exercise increased diameter of a fiber (and the force)
Range of fiber =
range of sarcomere x sarcomeres in series
Velocity of shortening of a muscle fiber
velocity of shortening of one fiber x sarcomeres in series
-longer muscle fibers have LARGER shortening range and FASTER shortening rates
Advantage of long fiber
-stretch/shortening spread out over many sarcomeres so that there is a smaller change in length of a single sarcomere (smaller decrease of tension)
Disadvantage of long fibers
does not increase the maximum force but does increase the amount of energy required
Isometric contraction
the muscle develops force at a constant length
Isotonic contraction
the muscle shortens under a constant load
Force-velocity relationship
-the steady state velocity of shortening depends hyperbolically on the load
IE: at isometric contraction the load is so heavy that the myosin are all involved in resisting the load and there are none available to shorten
-at very light loads there are more myosin available for shortening
