Physiology of Muscle Contraction

Question 1

List the names for muscle at the following levels: large groups of cells, a single multinucleate cell, organelle, molecular lines

Answer 1

Fascicle, myofibre, myofibril, myofilament

Question 2

How many thin filaments are adjacent to one thick filament?

Answer 2

6

Question 3

How many thick filaments are adjacent to one thin filament?

Answer 3

3

Question 4

In the sarcomere, which bands become shorter during contraction?

Answer 4

H and I

Question 5

List three proteins residing on thin filaments

Answer 5

F actin, tropomyosin, troponin

Question 6

Why is skeletal muscle sometimes referred to as “striated muscle”, and what is the basis of the striations?

Answer 6

Under the microscope, skeletal muscle has a “striped” appearance. The stripes extend perpendicular to the direction of contraction. The stripes (A bands and I bands) are a function of where the myosin/thick filaments are – wherever there are thick filaments is darker or more dense staining.

Question 7

What ions (3) travel across the membrane during the skeletal muscle action potential (include their direction and when they move)?

Answer 7

Na+ goes in during depolarisation, K+ goes out during repolarisation, Ca2+ goes in during depolarisation

Question 8

What is the name of the process that connects the action potential to muscle contraction?

Answer 8

Excitation-contraction coupling (EC-coupling)

Question 9

What is a thick filament made of

Answer 9

Myosin, with heads sticking out regularly, include bare zone

Question 10

What are microscopic structures that anchor the thick and thin filaments?

Answer 10

Thick filaments are anchored by M band (minor proteins of thick filament), thin filaments are anchored to z disc

Question 11

Assuming the thick and thin filaments are in place, what other regulatory molecules (that are not necessarily present) are required to allow the actin-myosin crossbridge cycle to continue?

Answer 11

ATP and calcium

Question 12

What chemical event triggers depolarisation of a skeletal muscle cell?

Answer 12

Acetyl choline binding to its nicotinic receptor

Question 13

What two events lead to E-C coupling in skeletal muscle.

Answer 13

Depolarisation of the cell membrane (and thus T tubules) causes calcium release from the terminal cisternae of the sarcoplasmic reticulum into the cytosol.

The calcium then leads to troponin moving tropomyosin such that the myosin heads can interact with the thin filaments

Question 14

Explain E-C coupling in skeletal muscle at the molecular level

Answer 14

Depolarisation alters the conformation of the L-type calcium channel, this is physically connected to Ryanodine receptor (the channel that allows movement of calcium out of the SR), the ryanodine receptor opens, and calcium is released into the cytosol near the myofibrils

Question 15

Name the subunits of troponin and tropomyosin, connections between them, and their function in skeletal muscle regulation

Answer 15

Tropomyosin physically occludes the myosin interaction site on the thin filaments, so it is a key regulatory protein of skeletal muscle contraction.  It has one peptide subunit
Troponin T (TnT) is connected to tropomyosin and can pull tropomyosin out of its blocking site, TnC is the calcium binding subunit between TnT and TnI, and when it binds calcium it changes conformation and causes TnT to pull tropomyosin, TnI is fixed to the thin filament so that when the entire troponin complex changes conformation, it moves the tropomyosin.

Question 16

Describe the differences between troponin molecules in skeletal, cardiac and smooth muscle

Answer 16

Skeletal muscle troponin has 3 subunits: TnI, TnC and TnT. Cardiac muscle troponin also has 3 very similar subunits, but cardiac TnC binds 3 Ca2+ rather than 4 (which is what happens in skeletal).
Cardiac and skeletal TnC can be distinguished by antibody tests such as elisa’s. The antibodies used for clinical troponin tests are specific for troponin from cardiac muscle (TnI or TnT), so these detect MI rather than rhabdomyolysis.
Smooth muscle does not have troponin (or tropomyosin), and its regulation of contraction is completely different from striated muscle.

Question 17

Where does the cross bridge cycle stop if there is no ATP?

Answer 17

Just after the power stroke, while the actin and myosin are still connected.

Question 18

Put the following cross bridge cycle steps in order (starting with Actin and myosin associate): Myosin head goes to high energy position (cocked), Actin and myosin dissociate, Myosin hydrolyses ATP, ATP binds to myosin, ADP released, Pi released by myosin, Power stroke,

Answer 18

Actin and myosin associate > Power stroke > ADP released, ATP binding > Actin and myosin dissociate > Myosin hydrolyses ATP > Myosin head goes to high energy position (cocked) >Pi released by myosin.

Question 19

If the sarcomere’s force decreases as the muscle is stretched, what position is the muscle in and what is the molecular mechanism for the reduction in force?

Answer 19

The sarcomere is stretched beyond optimal. Stretching is resulting in reduced overlap of the myosin heads of the thick filaments with the thin filaments

Question 20

If the sarcomere’s force increases as the muscle is stretched, what position is the muscle in and what is the molecular mechanism for the increase in force?

Answer 20

The sarcomere is contracted beyond optimal. Stretching is resulting in reduced overlap of the thin filaments from the other side of the sarcomere, which are interfering with the thick-thin filament interactions

Question 21

How is contraction stopped?

Answer 21

After the action potential ends, it is possible to begin the process of reducing intracellular calcium, which would allow tropomyosin to resume its inhibitory position on the thin filament.
Calcium is removed primarily by being pumped back into the sarcoplasmic reticulum; some calcium is pumped out through the plasma membrane

Question 22

What are the molecules responsible for stopping contraction?

Answer 22

Repolarisation is driven by K+ flowing out via K+ channels.
Calcium is removed primarily by being pumped back into the sarcoplasmic reticulum by a Ca2+ ATPase called SERCA. The small amount of calcium pumped out via the plasma membrane goes through a Na+/Ca2+ exchanger.
When intracellular calcium decreases, troponin loses its calcium, which allows tropomyosin to re-occupy a position that blocks antin-myosin based contraction.

Question 23

Explain how Creatine functions to maintain homeostatic levels of ATP intracellularly.

Answer 23

Creatine phosphate acts as a “energy buffer” for ATP; when a lot of ATP is formed, instead of accumulating ATP, the cell transfers the high energy phosphate bonds to creatine phosphate (ie the cell accumulates creatine phosphate) using the enzyme creatine kinase, whilst ATP levels remain at homeostatic levels.

Question 24

What is the difference between intrafusal and extrafusal muscle fibres.
(Structural + Functional)

Answer 24

Structural: intrafusal fibres are inside of the collagen sheath in the belly of the muscle. Extrafusal fibres are outside that sheath.

Functional: intrafusal fibres function as sensory organs to determine muscle length for proprioception. Exrafusal fibres generate muscle force via contraction.

Question 25

Name two types of sensor tissues in skeletal muscle that are important for reflexes and for each one list the type of reflex it controls and whether it is positioned in series or in parallel with extrafusal muscle fibres.

Answer 25

Muscle spindle vs golgi tendon organ Spindle: stretch reflex, in parallel Golgi tendon organ: tendon reflex, in series

Question 26

Explain why as the sarcomere shortens to its minimum length, the force generated diminishes.

Answer 26

The thin filaments from the opposite side of the sarcomere interfere with actin-myosin contraction reaction. At very short sarcomere lengths, the thick filament may hit the z-disc (at the end of the sarcomere)

Question 27

Describe the difference between muscarinic and nicotinic cholinergic neurotransmission, and list some agents that are relevant for the neuromuscular junction?

Answer 27

Both receptors respond to Ach. The nicotinic receptor is specific to nicotine and transmits the signal via cation entry, whereas the muscarinic receptor is specific to muscarine (and is blocked by atropine) and works via G-proteins. Anaesthetists block nicotinic receptors to create muscle relaxation (eg rocuronium), which can be important for intubation.

Question 28

List the four steps of actin-myosin cross-bridge cycling.

Answer 28

Release of myosin by actin Activation of myosin by ATP cleavage Activated myosin binds actin Power stroke

Question 29

List (or draw) the relevant steps in the actin-myosin cross bridge cycle where ATP, ADP and calcium come into play

Answer 29

ATP must bind to myosin in order for it to release of myosin by actin ATP cleavage leads to the Activation of myosin Intracellular calcium levels control whether Activated myosin can bind actin; during this reaction phosphate is released by myosin ADP is released just after the Power stroke

Question 30

What is the difference between isotonic and isometric force generation.

Answer 30

Isometric force generation implies that the muscle does not change size; this means that the force generated is not sufficient to move the resistance, and that tension is increasing. Isotonic force implies that the tension (ie force) generation is constant; this implies that the muscle is successfully moving against the resistance, and that no further recruitment of muscle fibres is needed.

Question 31

Explain how force generation increases when catching a ball.

Answer 31

Voluntary increases in muscle force generation depend on increasing neural activity. As neural activity increases, more motor units are recruited. The order of recruitment is determined by the size principle, which dictates that motor units recruited later control more muscle fibres and can generate more force than the motor units recruited at the beginning. During catching a ball, contraction follows the opposite order to concentric contractions. Insufficient eccentric muscle contraction is initially eccentric and later becomes both isometric & isotonic.

Question 32

Explain how one muscle can be required to perform both concentric and eccentric contraction during a single activity, using the example of the action of the quadriceps femoris during the long jump

Answer 32

During concentric contraction muscle length shortens during force generation. During eccentric contraction muscle length lengthens during force generation. During take off in the long jump, the knee extends, and the force to drive the take off is provided by concentric contraction of the quadriceps, which shorten. During landing, in order to break the fall, the bent knee must resist the force of the ground causing the knee to flex. To prevent flexion, the quadriceps generate force; however, the muscle does not shorten — it lengthens because the force of landing is greater than the force being generated by the muscle.

Question 33

Explain how the size principle determines muscle activity, using the example of the action of the quadriceps femoris during landing in the long jump

Answer 33

The size principle means that for muscle to generate increased force, recruitment of motor units proceeds from smaller (weaker) to larger (more powerful) motor units, until sufficient force is generated to achieve the desired outcome (as determined by proprioception). During landing in the long jump, extending the knee too early will damage the joint rather than help brake the landing. Ideally, the muscle can be used to absorb the force of the fall while the knee is partly flexed and the quadriceps are attempting to extend the knee. This requires that the quadriceps generate enough force to partially break the fall, but not so much force that the knee extends into a locked position. The precise force needed is determined by proprioception, and when the force is insufficient (ie if the knee starts to flex too much) the size principle results in recruitment of more and large motor units to generate force to oppose the flexion of the knee.

Question 34

Briefly explain what is eccentric contraction of muscle.

Answer 34

When force generation is accompanied by overall lengthening of the muscle.

Question 35

Give two examples of eccentric contraction of muscle.

Answer 35

Catching a ball. | Landing at the end of a long jump

Question 36

List six differences principles of stretch reflexes that are different to tendon reflexes

Answer 36

``` Increases muscle force Responds to stretch Sensor is muscle spindle Sensor in belly of muscle Thus, Sensor is in parallel with muscle Sensor sensitized by gamma motor neurons ```

Question 37

List six differences principles of tendon reflexes that are different to stretch reflexes

Answer 37

Decreases muscle force Responds to tension Sensor is golgi tendon organ Sensor is in tendon Thus sensor is in series with muscle fibres Sensor is not sensitized by gamma motor neurons

Question 38

Give an example of a muscle where you would expect a predominance of slow-twitch fibres and another muscle where you would expect predominance of fast-twitch fibres.

Answer 38

Postural muscles would be higher in slow twitch fibres. An example would be the soleus. Non-postural muscles would be more likely to be fast twitch fibres. This could include eye muscles or hand muscles.

Question 39

Describe slow-twitch fibres.

Answer 39

Slow twitch fibres are slower to act, more likely to be coloured and due to higher myoglobin concentrations more mitochondria. They use more oxidative phosphorylation to generate energy, and they are more fatigue resistant. As individual fibres, they generate less force per unit of cross-sectional area. They store a larger percentage of their energy as triglycerides

Question 40

Describe fast-twitch fibres.

Answer 40

Fast twitch fibres are non-oxidative. They have less myoglobin and therefore may be “whiter”. They get more energy from glycolysis. Their speed of activity will be faster. Their maximum tension produced will be larger. They will have less fatigue resistance. Their speed of calcium reuptake will be faster. Energy is stored as glycogen and creatine-phosphate

Question 41

Explain the differences between a motor unit and a muscle fibre.

Answer 41

A motor unit is a collection of muscle fibres and the neuron that innervates all of them. The neuron determines all of the fibre types for that motor unit. A muscle fibre is a single cell. each fibre can be fast twitch or slow twitch (the fibre type). Motor units can comprise many fibres to produce strength or a few fibres for accuracy. All the fibres in a single motor unit are of the same fibre type. The neuron and its activity determine the typology of the muscle cells.