EC coupling and skeletal muscle contraction Flashcards
what triggers contraction in all types of muscle
increase of intracellular Ca2+
what type of receptors are present at NMJs
ACh receptors
what are the levels of organization in skeletal muscle
whole muscle -> muscle fiber (single cell) -> myofibril -> thick and thin filaments -> myosin and actin (protein molecules)
what is the main component of thin filaments in skeletal muscle ?
actin
what is the main component of thick filaments in skeletal muscle ?
myosin-II molecules
what are the main features of a skeletal muscle cell ?
-elongated and cylindrical
- 10-100um in diameter and up to 75 cm in length
- multiple nuclei
abundance of mitochondria
what is a myofibril
specialized contractile elements that extend the entire length of the muscle fiber
how many myofibrils does a single muscle fiber contain
100-1000
sarcomere
smallest functional unit in the muscle
H - zone
portion of A band in which the is no over lap of thick and thin filaments
M- line
center of the sarcomere, holds thick filaments in place
A band
considered to be the dark band of the sarcomere
I band
light band of sarcomere, located between two myosin and contains only the actin filaments of the neighboring sarcomeres
Z-line
flat cytoskeletal disc which marks the boundary of a sarcomere
what are the main features of thin filaments
- mainly actin
- also made up of troponin and tropomyosin
- double stranded a helices
- actin molecules have binding sites for myosin
tropomyosin
prevents myosin cross bridges from attaching to thin filaments
what are the three subunits of troponin ?
-Troponin T : binds to single molecule of tropomyosin
- Troponin C : binds to Ca2+
- troponin I : binds to actin and inhibits contraction
what are the functions of troponin
stabilizes tropomyosin when Ca2+ levels are low and inhibits contraction
how many actin monomers does a single tropomyosin molecule interact with
7
how many tropomyosin molecules does each heterotrimer of troponin interact with
1
where is tropomyosin located in the muscle fiber?
the thread like structures sit within the grove formed by the alpha helix of the thin filament and covers myosin binding sites
what is each myosin-II molecule composed of ?
each molecule is a double trimer with : 2 intertwined heavy chains, 2 regulatory light chains and 2 alkali (essential) light chains.
what are the three regions of the myosin heavy chains
tail, hinge and head
what is the structure of the tail portion of the myosin molecules
a-helices that are intertwined
the hinge region of the myosin molecule…
opens to form two globular heads
what do the head regions of the myosin molecules give rise to ?
cross-bridges between thick and thin filaments of the sarcomere
what are the two binding sites on the myosin heads ?
1) actin binding site
2) site for binding and hydrolyzing ATP
what is the function of the alkali light chain ?
stabilizes the myosin head region
what is the function of the regulatory light chain ?
regulates ATPase activity of myosin
what regulates the activity of the regulatory light chains ?
they are regulated through phosphorylation by kinases
why does an increase of intracellular Ca2+ trigger muscle contraction ?
removes the inhibition of crossbridge cycling
what is the normal resting levels of intracellular Ca2+ ?
10^-7 M
To what levels does intracellular Ca2+ levels rise to upon stimulation ?
greater than 10^-5M
what does Ca2+ bind to in muscle fibers
Troponin C
how many calcium binding sites does Troponin C have ?
2x high affinity and 2x low affinity
high affinity Ca2+ binding sites participate in …
binding troponin C to the thin filaments but Ca2+ binding to these sites does not change during muscle activation
what does the binding of Ca2+ to the low affinity binding sites on troponin C induce ?
conformational change in the troponin complex
Describe the conformational change that happens to the troponin complex
-Troponin I shifts allowing tropomyosin to move
- Via Troponin T, tropomyosin is moved away from the myosin-binding site on actin and into the actin grove
- this means that the myosin head can now interact with actin and engage with Cross bridge cycling
what are the 5 steps of cross bridge cycling ?
1)ATP binding
2) ATP hydrolysis
3) cross bridge formation
4) release of Pi from myosin
5) ADP release
what does ATP binding to the myosin head cause ?
dissociation of the actin- myosin complex ( released state)
what does ATP hydrolysis cause in then cross-bridge cycle ?
myosin heads to return to their resting conformation
what triggers the power stroke state in the cross-bridge cycle ?
The release of Pi
describe the sliding filament mechanism
-thin filaments on each side of a sarcomere slide inwards over stationary thick filaments.
-As they slide inwards the thin filaments pull the Z lines closer together so the sarcomere shortens.
-All sarcomeres throughout the muscle fiber shorten simultaneously, the entire fiber shortens
what happens to the A band during contraction?
determined by thick filaments so stays the same width
what happens to the I band during contraction ?
thin filaments not overlapping thick so band width decreases
what happens to the H zone during contraction
width decreases
what happens to the distance between Z lines during contraction ?
decreases
do the length of the thin and thick filaments shorten during contraction
No
how long after death does rigor mortis begin
3-4 hours
how long after death is rigor mortis complete
12 hours
describe the process of rigor mortis
- intracellular Ca2+ begins to rise
- Ca2+ lets regulatory proteins move aside allowing cross bridges to form, that were already charged with ATP prior to death
- dead cells cannot produce ATP so actin and and myosin remain attached
- rigor mortis subsides over the next several days when the protein involved start to degrade
what is the process by which excitation triggers the increase of intracellular Ca2+ known as ?
excitation-contraction coupling (E-C) coupling
how are Action potentials spread to the interior of skeletal muscles ?
traverse tubules (t-tubules)
where are t-tubules located on the muscle ?
at the junctions between A and I bands between two sarcoplasmic reticulum
what is the intracellular store for calcium
sarcoplasmic reticulum
what is the “triad”
T-tubule between two sarcoplasmic reticulum
what part of the SR is adjacent to the t-tubules ?
terminal cisternae
what triggers a release of Ca2+ from the SR into the cytosol ?
spread of an action potential down a T-tubule
what are the membrane proteins on the t- tubules known as and what do they do ?
dihydropyridine receptors (DHP) and they serve as voltage sensors
what does the depolarization of t-tubules trigger ?
it activates the DHP receptors which in turn trigger the opening of Ca2+ release channels (ryanodine receptors) in the adjacent terminal cisternae, releasing Ca2+ into the the cytosol
why are Ca2+ release channels also known as ryanodine receptors ?
they are locked in the open position by the plant protein ryanodine
what spans the gap between the SR and t-tubule
foot-proteins that serve as Ca2+ release channels
What is CICR and what does it play a critical role in ?
Ca2+ induced Ca2+ release, it is not necessary for contraction in skeletal muscle but plays a critical role in E-C coupling in cardiac muscle
what removes Ca2+ from the cell ?
Na-Ca exchanger and Ca2+ pump (Ca2+ is dependent on hydrolysis of ATP)
what concentrates Ca2+ within the Sarcoplasmic reticulum
Calreticulin and Calsequesterin
how does Ca2+ enter the Sarcoplasmic reticulum ?
Ca2+ pumps
what is the total duration of a Ca2+ pulse in a skeletal muscle fiber ?
1/20 of a second
if prolonged contraction of a muscle is required what must occur
a series of calcium pulses must be initiated by a continuous series of repetitive action potentials
By what factor does intracellular Ca2+ increase by when there is full excitation of the T-tubule/SR system
500-fold increase
how is the contractile process turned off ?
Ca2+ is returned to the SR when electrical activity stops via Ca2+-ATPase pumps
and thin filaments return to their resting position
