20-01-22 - Force Generation, Energy usage and Fibre types Flashcards
Learning outcomes
- Describe the energy sources available to skeletal muscle and the role of ATP in contraction
- Describe events during cross bridge formation to generate sarcomere shortening
- List the different types of skeletal muscle fibre and compare & contrast their main biochemical and physiological properties
- Define the length-tension relationship and load-velocity relationship of muscle contraction
What are the 4 roles of ATP in the muscle?
• Role of ATP in the muscle:
1) Membrane potential
• Na+/K+ ATPase in the sarcolemma maintains the Na+ and K+ gradients
• This allows the production and propagation of action potentials
2) Ca2+ gradient
• Active transport of calcium ions into the sarcoplasmic reticulum, lowering the cytoplasmic calcium concentration
3) Power stroke
• Hydrolysis of ATP by myosin
• ATPase energises the cross-bridge formation, enabling sarcomere shortening and contraction
4) Cross Bridge Dissociation
• Binding of ATP to myosin dissociates cross-bridges bound to actin
How is ATP generated?
How much ATP do muscles contain?
What are the 3 methods of skeletal muscle energy metabolism?
- ATP is generated in all calls via respiration (aerobic and anaerobic)
- Muscles contain approximately 4 mM of ATP, which is enough for about 2 seconds of contraction
- Methods of skeletal muscle energy metabolism:
1) Creatine phosphate
• Rapid ATP formation at the onset of muscle contraction
• Molecule unique to muscle cells
• In a resting cell with plenty of ATP, ATP will donate its phosphate to ATP
• Creating phosphate can readily give up its phosphate to ADP to generate ATP in a process separate from cellular respiration mechanisms
• Stores of CP in the muscle provide enough energy for approximately 8 seconds of contraction
2) Glycolysis
• Anaerobic
• Fast rate of ATP generation from glucose/glycogen for approximately 1 minute until production until the production can’t keep up with the demands of the muscle
• Most carbs converted to glucose to be used in glycolysis
• Normally products of glycolysis will go on to oxidative phosphorylation to generate maximum number of ATP per molecule of glucose
• During a quick sprint, there is not sufficient time for oxidative phosphorylation to take place, and therefor we rely on ATP being generated by glycolysis
• The limiting step in glycolysis is the build-up of lactic acid, which can inhibit muscle function
3) Oxidative phosphorylation
• Aerobic
• Supplies the most amount of ATP per glucose molecule, and other fuel types, such as fats and proteins
• Can power contraction for hours
• Oxidative phosphorylation takes molecular oxygen and reduces it to water to generate huge amounts of ATP
What are the 6 stages of cross bridge formation and the power stroke in skeletal and cardiac muscle?
What is regulation of cross-bridge formation due to?
• Steps of cross bridge formation and power stroke in skeletal and cardiac muscle:
1) ATP binding
• ATP binds to myosin head, causing dissociation of the actin-myosin complex
2) ATP hydrolysis
• ATP is hydrolysed, causing myosin heads to return to their resting conformation
3) Cross-bridge formation
• A cross-bridge forms and the myosin head binds to a new position on actin
4) Release of Pi from myosin
5) Power stroke
• A conformational change in the myosin head causes the power stroke
• The filaments slide past each other
6) ADP is released
• Regulation of cross bridge formation is due to availability of myosin binding site on actin, via Intracellular calcium concentration and tropomyosin
What is rigor mortis?
When does it begin, peak and last till?
Describe the 9 steps of rigor mortis?
- Rigor mortis refers to the muscular stiffness that occurs after death (post-mortem rigidity)
- Rigor mortis can begin approximately 4 hours after death, peak at approximately 13 hours, and lasts approximately 50 hours
1) Death
2) Ca2+ pumps no longer function
• Energy required to pump calcium back into SR is not there
3) Ca2+ leaks into the cytosol from the SR
4) Ca2+ binds troponin
• This causes tropomyosin to reveal the myosin binding sties on actin
5) Myosin binds to actin
• This occurs if there is ATP still there
• There will be some after death
6) ATP production ceases
• No more ATP to bind to the myosin head, so the myosin can’t be released from the actin
7) No more ATP present to break cross-bridges
• Muscle is in rigor position, where the myosin head and actin are bound together and can’t be released
8) Muscles become stiff
9) Proteolytic enzymes work within a few days
• Proteolytic enzymes break down cross-bridge formations
• Muscles relax after this point
What decides the function of skeletal muscles?
What are the 3 different kinds of myosin isoforms in skeletal muscle fibres ?
How does the histology of different muscle fibres vary?
How is a fibre determined to be fast or slow twitch?
How does colour of muscle give indication to the type of muscle fibres they contain?
What is this different in colour due to?
How is ATP generated in muscle that contained primarily fast or slow twitch muscle fibres?
- The function of skeletal muscles is decided based on the different myosin isoforms they contain.
- The 3 kinds of myosin isomers in skeletal muscle fibres:
1) Type 1 – slow twitch muscle fibres – white in histology
2) Type IIA – intermediate – dark purple in histology
3) TypeIIB/11X (in humans) – fast twitch muscle fibres – light purple in histology
- A fast twitch or slow twitch muscle fibre is determined by the ability of that fibres myosin to hydrolyse at different speeds
- The redder the muscle, the more type 1 slow twitch muscle fibres the muscle contains
- The lighter the muscle, the more type 11B/11X fast twitch muscle fibres it contains
- This different in colour is due to the oxygen pigment myoglobin, which is a similar molecule to haemoglobin, in that it can gold oxygen
- The more the myoglobin present, the refer the tissue, because more energy is needed to generate energy via oxidative phosphorylation
- Muscles that contain mostly fast twitch muscle fibres have low myoglobin, and generate most of their ATP via glycolysis, which can be undertaken in anaerobic conditions
- Muscles that contain mostly slow twitch muscle fibres have high myoglobin, meaning they are endurance muscle that contract regularly, so they generate their ATP via oxidative phosphorylation, which is undertaken in aerobic conditions
How are skeletal muscle fibres classified?
What are the 3 different categories upon which they are classed?
Based on this, what are the differing physiological features in oxidative and glycolytic fibres?
• Skeletal muscle fibres are classified based on mechanical and metabolic characteristics
1) Maximal velocities of contraction (fast or slow)
2) Major pathway for generation of ATP
• Down to the enzyme activity of myosin heads that bind and hydrolyse ATP
• Can be oxidative of glycolytic
3) Different muscle types have different isotypes of myosin ATPases
• Different proportions of fast, slow, and intermediate fibres within a single muscle lead to different maximal rate of cross-bridge cycling
• Based on this, the following are greater in slow oxidative fibres:
1) Greater number of mitochondria – involved in oxidative phosphorylation and generation of ATP
2) Greater amount of myoglobin
3) Greater number of blood vessels and capillaries for oxygen supply
• The following are greater in fast glycolytic fibres:
1) Greater store of glycogen, glycolytic enzymes, creatine phosphate (muscles used sporadically will have more of these)
2) Greater size
What do each of the 3 muscle fibres combine?
What do all skeletal muscles contain?
How does this vary between individuals?
1) Type 1 slow oxidative fibres
• Combine slow myosin ATPase activity with high oxidative capacity
• Slow twitch contraction and slow hydrolysis of ATP relative to fast twitch
2) Type IIA fast-oxidative glycolytic fibres
• Combine fast myosin-ATPase activity with high oxidative capacity and intermediate glycolytic capacity
3) Type 11B/11X (in humans) Fast-glycolytic fibres
• Combine fast myosin ATPase activity with high glycolytic capacity
- All skeletal muscle contains all of these fibres, but in varying proportions
- These proportions are genetically determined, vary between individuals, and can not be changed
Where do muscles receive stimuli from?
What does each myofiber have?
Why does duration of contraction differ?
What are 3 different muscles with different duration of contraction?
How does the action potential compare among these muscles?
- Muscles receive stimuli from a motor neurone
- Each myofiber/muscle cell has its own neuromuscular junction to trigger contraction
- Duration of contraction differs depending on fibre type composition of individual muscles
- Ocular muscle – extremely rapid contraction
- Gastrocnemius – moderately rapid contraction
- Soleus muscle – relatively slow contraction (full of slow twitch muscle fibres constantly contracting to maintain posture
- The action potential is the same in all of these muscles, but the rate at which the ATP is being hydrolysed/metabolised is different, hence the differing length of contraction
What does a single motor neurone innervate?
What is a motor unit?
What do small muscle with fine control generally have?
What is an example?
What do large muscle generally have?
What is an example?
- A single motor neurone innervates multiple muscle fibres
- A motor unit is all the fibres innervated by a single neuron, with neuromuscular junctions scattered throughout the muscle
- Generally, small muscles with fine control have more nerve fibres for fewer muscle fibres e.g laryngeal muscles
- Conversely, large muscle may have hundreds of fibres in a motor unit e.g soleus
What are the two things force of contraction depends on?
How are motor units recruited?
What do small motor units innervate?
How excitable are they?
How do they conduct action potentials?
What are they typically made up from?
How excitable are larger motor units?
How do they conduct action potentials?
What are they typically made up from?
What is the size principle?
• Force of contraction depend on:
1) Number of motor units recruited
2) Frequency of action potentials sent to the muscle
- Motor units are recruited in a progressive way, from smallest (weakest) to largest (strongest)
- Small motor units innervate the fewest number of muscle fibres, with the smaller the motor unit, the more likely they are to be initiated at a lower frequency
- Small motor units are more excitable
- They conduct action potentials more slowly
- Small motor units typically consist of neurons innervating type 1 (slower) muscle fibres
- Large motor units are less excitable
- They conduct action potentials more rapidly
- Large motor units typically consist of neurons innervating type II (fast) fibres of large muscle that require a greater degree of power
- The size principle is that the smaller motor units will be recruited first, causing a weak contraction within the muscle
- The more motor units that are stimulated, the greater the force of contraction will be
What does the strength of muscle contraction depend on?
What occurs when greater force is required according to the size principle?
What Is muscle tension?
What is the load?
What does the muscle have to overcome to shorten?
- The strength of muscle contraction varies depending on demands placed on them
- According to the size principle, as greater force is required, more motor units, and larger motor units are recruited e.g picking up 1kg compared to 10kg
- Muscle tension is the level of force generated when the muscle cell contracts
- The load is the force exerted by an object to be moved
- The muscle has to overcome the load force (resistance) in order to shorten
Describe the 4 stages of summation of muscle fibres
A) One action potential leads to a single skeletal muscle twitch (lasting about 25-200msecs)
B) As muscle twitch far exceeds duration of action potential, it is possible to initiate a second action potential before the first contraction has subsided, with the 2nd twitch stronger than the first
• This is due to higher cytoplasmic calcium concentration.
• More calcium in the cell, which enables more myosin to bind with the actin, leading to greater force.
• This is known as summation
C) Multiple actions potentials occur close together, resulting in frequency summation
D) This results in tetanus, which is when the stimulation frequency is so high, that the individual contractions fuse
• There is no relaxation between
• Muscle contractions to maximum tension/strength to try and lift the load
What is isotonic contraction?
What is isometric contraction?
- Isotonic contraction is muscle shortening will occur if peak tension is greater than load force
- Isometric contraction is when muscle stimulation will increase tension, but no shortening will occur if the load force is greater than muscle peak force
What is the length-tension relationship related to?
What does this cause?
Describe the 4 points on this graph
- Length-tension relationship is directly related to the overlap between actin and myosin within the sarcomere
- This causes different amount of tension to be generated at different degrees at overlap
- Point A - Zero tension is no actin and myosin overlap, with no cross-bridges being formed
- Point C - Maximum tension is when the actin overlaps all of the cross bridges on myosin (but not yet reached m-line) – full tension is maintained until point B
- Point B – Maximum tension when the ends of two actin filaments begin to overlap each other, in addition to overlapping myosin
- Point A – as the sarcomere shortens further, the two Z discs abut (touch) the myosin – the tension drops to zero, and the sarcomere has contracted to the shortest length
How rapid is contraction with no load?
What occurs when loads are applied?
What occurs when the load equals the maximum tension a muscle can exert?
- Full muscle contraction is rapid with no load (approximately 100ms)
- When loads are applied, contraction velocity decreases with increasing load (ie can pick up 1kg faster than 10kg)
- When the load equals the maximum force or tension that a muscle can exert, the velocity of contraction is zero
- This is isometric contraction, where there is no shortening of the muscle, and the load cannot be moved
