S1: Contractile Mechanisms and Energy Sources Flashcards
Which muscles are striated?
- Skeletal muscle is regularly striated
- Cardiac muscle is striated and less regulated
What is a sarcomere?
Distance between two z lines
Name the thin filament in a sarcomere
Actin is the thin filament
Name the thick filament in a sarcomere
Myosin is the thick filament
What is the I band in a sarcomere?
The distance between where myosin ends and the next begins
What is the A band in a sarcomere?
The length of the myosin
What is the H zone?
The gap between actin filaments
What is the light band and dark band?
Light band is where there is only one type of protein present as light can pass through actin (thin filament)
Dark band is where the thin filaments over lap with the thick filament (myosin) and light is unable to pass through
Explain how there is transduction in muscle contraction
The energy put into muscle contraction is chemical but the effect produced is mechanical so there is transduction (change in form of energy)
What is the sliding filament hypothesis?
When the muscle contracts, the overlap increases (dark band) and the thin filaments slide over the thick ones.
What is the organisation of actin in muscle cells?
Actin forms a double helix filament that is stable. It is also surrounded by tropomyosin and has troponin complexes regularly spaced along the actin filament.
What is the organisation of myosin II in muscle cells?
Myosin II forms the thick filament and is constructed from myosin diamers. These form the tail which has a double helix structure and the head where another myosin molecule can join by the tail.
The tail and back part of the head are called ‘heavy chains’ while the front part of the head is associated with ‘light chains’
How does the actin move along the myosin?
The cross bridge cycle
Explain the crossbridge cycle
- When muscle is relaxed, the myosin is in the ‘rigor state’ attached to the actin filament but there is no movement
- To initiate movement, ATP is added to the myosin head and this detaches the myosin head from the actin
- The ATP then undergoes hydrolysis and the energy released is used to tilt the myosin head back
- When the phosphate is released, the myosin binds to another subunit on the actin further up
- ADP is then released and this causes a power stroke whereby the myosin head tilts back to the rigor state (rigor conformation) and this causes the actin to slide along the myosin initiating contraction.
What is the ‘rigor state’?
This is when the muscle is relaxed.
The myosin is attached to the actin filament and there is no movement - rigor state
What is added to the myosin head to initiate movement in crossbridge cycle?
ATP
What happens when ATP is added to the myosin head in crossbridge cycle?
The myosin head detaches from actin
ATP undergoes hydrolysis in the crossbridge cycle
What is the energy released used for?
The energy is used to tilt the myosin head back.
When does the myosin head bind to a different subunit on actin (further up)?
When the phosphate is released
What is a power stroke?
When ADP is released, the myosin head tilts back to the rigor state (rigor conformation) and this causes actin to slide along myosin.
What is the common regulator of muscle contraction (what signals the muscle to contract)?
The secondary messenger Ca2+
What blocks the crossbridge cycle from occuring until Ca2+ comes along?
Tropomyosin
Compare the concentration of Ca2+ in the ECF and SR to cytosol?
Why are the differences significant?
The concentration of Ca2+ in ECF and SR is high (1-2mM)
The concentration of Ca2+ in cytosol (50-100nM)
Only a small rise in concentration in the cytosol is enough for Ca2+ to act as a secondary messenger
How does Ca2+ enter the cell?
Through VGCCs upon depolarisation and coupling of VGCCs and RyR releases calcium stores from SR
How does the SR allows muscles to contract synchronously?
The SR actually wraps itself around the myofibrils allowing the muscle to contract synchronously, with Ca2+ being released from the SR that goes straight into the myofibrils.
Explain calcium induced calcium release (cardiac)
When sarcolemma is depolarised, the dihydropyridine receptor which has a Ca2+ channel allows small amounts into the cell, this then causes the ryanodine receptor (in heart and skeletal muscle only) on the SR to release Ca2+ into the cytosol.
What does the troponin sensor do?
It senses the rise in calcium in skeletal and cardiac muscle
What is the organisation of the troponin complex in the absence of Ca2+?
Troponin complex sits on top of the tropomosin and prevents the myosin head from binding to the actin.
Name the three parts that troponin is composed of
TnT
TnC
TnI
What does TnT do?
Binds to tropomyosin
What does TnC do?
Binds to the calcium (is the troponin sensor that senses rise in calcium)
What does TnI do?
This is the Inhibitor
How does calcium remove inhibition of troponin complex?
When Ca2+ binds to the TnC, it causes the other part of the TnC to bind to one part of the inhibitor and this results in a conformational change which removes the inhibition allowing the muscle to contract.
What is thin filament activation?
Cardiac/Skeletal
The removal of the inhibition of troponin complex allowing myosin access to actin to allow contraction
What is Mg+ used for in contraction?
Mg+ is needed for the catalysis of ATP hydrolysis.
In ATP the phosphates are called alpha, beta, gamma.
Mg+ forms a complex with them, binding between alpha and beta phosphates
Compare Ca2+ influx mechanisms in cardiac and skeletal muscle
Cardiac: Calcium induced calcium release!
DHPR mediates Ca2+ influx which activates RyR causing more influx of Ca2+
Skeletal Muscle: Action potential on t-tubule activates VGCCs. Direct coupling (when one opens the other opens) between VGCCs and RyR on sarcoplasmic reticulum (SR) –> Activates RyR via physical interaction
What regulates contraction in smooth muscle?
Thick filament as there is no troponin complex on the actin
How is intracellular levels of Ca2+ increased in smooth muscle?
- depolarisation of smooth muscle activating VGCC
- Gq mediated pathways where IP3 binds to IP3 receptor on SR which causes it to release Ca2+ (M3 receptor)
What is the Ca2+ sensor in smooth muscle?
As smooth muscle doesn’t contain troponin complex and therefore doesn’t contain TnC
Calmodulin
How many places can calmodulin bind to Ca2+?
4 places
How is calmodulin different form TnC?
When calmodulin is inactive it is free to move around unlike TnC
What happens when Ca2+ binds to calmodulin?
Calmodulin gets activated and a ca2+\caM complex is formed.
This complex activates myosin light chain kinase (MLCK) by binding to it.
What does activated MLCK do?
It phosphorylates the light chains of myosin which are on the myosin heads using ATP.
This activates myosin (myosin heads cannot bind until light chain is phosphorylated).
It is now able to hydrolyse ATP and the cross bridge cycle occurs
Compare what needs to happen to sarcomere before entering cross bridge cycle in smooth muscle and cardiac/skeletal
Smooth: actin is free but myosin needs to be activated (thick filament regulation)
Cardiac/skeletal: troponin complex inhibition needs to be removed to allow access the actin (thin filament regulation)
What is thick filament activation?
Smooth
When myosin chain is activated by MLCK
How does activated myosin enter crossbridge cycle?
It activates myosin ATPase so it can hydrolyse ATP
What is contraction terminated in smooth muscle?
Phosphatase removes phosphate and contraction stops
How is Ca2+ removed from the cell?
- active pumps pump Ca2+ back to ECF or SR stores
- 3Na+/Ca2+ exchange pumps uses concentration gradient of Na+ to get rid of Ca2+ (sodium enters the cell and calcium leaves)
Na+/K+ pump ensures that levels of sodium are regulated
ATP is used up very quickly when we contract muscle
What is another store of rapid energy use?
Creating phosphate
How does creatinine phosphate act as energy?
It donates a phosphate to ADO producing ATP which can be used
How are ATP levels , inorganic phosphate levels and creatinine phosphate levels before and during excerise?
ATP levels are kept relatively stable
Inorganic phosphate levels increase as they have been cleaved off from ATP
Creatinine phosphate levels decrease significant
What process kicks in after creatinine phosphate levels are depleted?
Anaerobic process producing small amounts of ATP relatively fast
What process kicks in after anaerobic process?
Aerobic process producing a consistent amount of ATP
What happens if we overdo anaerobic respiration?
Lactate is produced
The cori cycle deals with this
Compare speed of muscle contraction
Fastest
- skeletal
- cardiac
- smooth
Slowest
