13. E-C coupling and skeletal muscle contraction Flashcards
How much body weight is skeletal, smooth and cardiac muscle?
- skeletal; 40%
- smooth and cardiac; 10%
What triggers contraction?
an increase calcium ion concentration
What are the steps in skeletal muscle contraction?
- Ach receptors are concentrated in the NMJ
- Ach is released from the pre-synaptic nerve terminal and bind to nicotinic acetylcholine receptors at the NMJ
- These receptors are non-selective cation channels that open in response to Ach binding, causing depolarisation of the end-plate potential
- If EPP exceeds threshold, an action potential is generated (activated by opening of voltage gated sodium channels)
- Generation of an AP initiates a sequence of events leading to contraction
- Ach is rapidly inactivated by Acetylcholine-esterase
The reaction mechanism for the breakdown of acetylcholine when inactivated
Ach to Acetate and choline (inactive states) using acetylcholine esterase
Describe the structure and size of a muscle fibre
elongated and cylinder shaped, 10-100 micrometers in diameter
How are muscle fibres formed?
through the fusion of myoblasts (smaller cells)
What are features of a muscle fibre?
- multiple nuclei
- abundance of mitochondria
- striated
Myosin
- thick filaments
- A / dark band
- arranged in a circle (surrounded by 6 actin molecules)
Actin
- thin filaments
- I / light band
- arranged in a triangle (surrounded by 3 myosin molecules)
Myofibril
- 80% volume of a muscle fibre
- extend the entire length of a muscle fibre
- consist of thin and thick filaments
- 1 micrometer in diameter
Name the cytoskeletal components of myofibrils
- m line
- z line
- h zone
- sarcomere
- thin and thick filaments
M line
- centre of the sarcomere
- keeps A bands together
Z lines
- either side of the sarcomere (joins adjacent sarcomeres)
- keep I bands together
H zone
- centre of an A band
Sarcomere
smallest component of a muscle fibre that can be stimulated to contract
Cross-bridge section
- 3 dimensions
1. actin surrounded by 3 myosin
2. myosin surrounded by 6 actin
3. cross-bridge
Describe the levels of organisation in a skeletal muscle
- whole skeletal muscle (an organ)
- muscle fibre ( a single cell)
- myofibril (a specialised intracellular structure)
- thin and thick filaments (cytoskeletal elements)
- myosin and actin (protein molecules)
What are the 3 components of thin filaments?
- actin molecules
- troponin
- tropomypson
What are actin molecules?
binding sites for attachment of myosin to form cross-bridges
What is the main component of thin filaments?
double stranded alpha helix polymer of actin (F actin molecules)
What are the 2 regulatory protein molecules?
- tropomyosin and troponin
What are the 2 types of troponin and what do they do?
- Troponin c - binds to calcium ions
- Troponin I - bonds to actin and inhibits contraction
What happens when troponin c is not bound to calcium?
it stabilises tropomyosin in its blocking site over the actins cross-bridge binding site
What are the 2 components of myosin?
- heads of myosin heavy chain (hinge region)
- tail (tail region)
What are the binding sites on the heads of myosin?
- actin-binding site
- myosin ATPase site
What are the two chains on the myosin heads?
- alkali light chain
- regulatory light chain
What do the myosin heads form when bound to actin?
cross-bridges
How is activity of the chain regulated?
by phosphorylation of kinases
What site does the myosin head bind to the actin filament at?
the myosin binding site
Where does energy for the cycle come from?
through hydrolysis of ATP
Describe the cross-bridge cycle
myosin-II head binds to actin, the cross-bridge becomes distorted and myosin heads detach from actin
What happens when there is a decrease in calcium ion concentration?
it is a signal to cease cross-bridge cycling and relax
What happens when calcium levels are low/ high?
high - myosin can bind to actin
low - actin is blocked by troponin/ tropomyosin (actin-myosin interactions are blocked)
Describe the 1st step of cross-bridge cycling
ATP binding - ATP binds to myosin head, causing dissociation of the actin-myosin complex
Describe the 2nd step of cross-bridge cycling
ATP hydrolysis - ATP is hydrolysed, causing the myosin head to return to resting conformation
Describe the 3rd step of cross-bridge cycling
Cross-bridge formation - a cross-bridge forms and the myosin head binds to the new position on actin
Describe the 4th step of cross-bridge cycling
A phosphate is released, myosin heads change conformation, resulting in the power-stroke
Describe the 5th step of cross-bridge cycling
ADP is released
How does the sliding filament mechanism bring about contraction?
cross-bridge interaction between actin and myosin brings about contraction
What happens during contraction?
due to interactions between the thick and thin filaments, the filaments slide over each other but the length of the filaments themselves do not shorten
What happens to the A bands during contraction?
stay the same width
What happens to the I bands during contraction?
Thin filaments not overlapping thick so width decreases
What happens to the H zone during contraction?
Within A band, thick filaments not overlapping thin so width decreases
What happens to the distance between z lines during contraction?
decreases
What becomes shorter during contraction?
the H zone and I bands
What is ‘Rigor mortis’? and how long does it occur?
stiffness of death which begins 3-4 hours after death and completes in 12 hours
What happens following this death?
- Calcium ion concentration rises allowing the regulatory proteins to move aside, letting myosin heads bind to actin to form cross-bridges.
- dead cells cannot produce ATP and so actin and myosin, once bound, cannot detach
- after several days, the proteins involved start to degrade as rigorous mortis subsides
What is E-C coupling?
when excitation triggers an increase in calcium ion concentration which triggers contraction
Describe the structure of the sarcoplasmic reticulum
TRIAD;
- sarcoplasmic reticulum cistema
- Transverse tubule
- sarcoplasmic reticulum ecistema
What forms transverse tubules?
invaginations in the plasma membrane
What is the role of the sarcoplasmic reticulum?
to store intracellular calcium ions
What happens in the skeletal muscle when the T tubule depolarises?
leads to calcium ion release from the sarcoplasmic reticulum at the triad
Describe the 4 steps involved in a single fibre triad
- membrane depolarisation opens the L-type calcium channel
- mechanical coupling between the L-type calcium channel and the calcium release channel causes the calcium ion release channel to open
- calcium ions exit the SR via the calcium ion release channel and activate Troponin C, leading to muscle contraction/ cross-bridge cycling
What are present on each of the 4 calcium release channels on the post-synaptic membrane?
Feet projecting into the cytosol
What drugs block muscle contraction
Dihydropyridines (DHP) and ryanodine
Describe how calcium ions are removed from the cytoplasm and their uptake into the SR
- Na-Ca exchanger and Ca2+ pump in the plasma membrane both extrude CA2+ from the cell
- Ca2+ pumps sequesters Ca2+ within the SR
- Ca2+ is bound in the SR by calreticulin and calsequestrin
How is contraction terminated?
by uptake of calcium ions into the SR
How does muscle contraction continue?
it will continue as long as there is a high concentration of calcium ions in the cytosol
What is calreticulin present in?
smooth muscle
What is calsequestrin present in?
smooth, skeletal and cardiac
Excitatory “pulse of calcium” steps
- initiation (full excitation of t-tubules/ SR system causes the release of calcium ions
- increase in calcium levels
- immediately after, the SERCA-calcium depletes, causing a pump of calcium and reuptake of calcium into SR, contraction occurs
What is the latent period?
short period when stimulation of onset of contraction occurs
What is the contractile period/ how is it turned off
?
the re-uptake of calcium ions into the SR
What is the relaxation period?
the time from peak tension to relaxation
How does the SR take calcium ions into the cytosol?
it uses calcium-ATPase pumps, which actively transport calcium
wWhat filaments return to resting conformation after contraction?
thin
