Lecture 11 - Excitation-contraction coupling

Question 1

Skeletal muscle

Answer 1

Epimysium is the outer connective tissue layer that surrounds a muscle
Perimysium is the connective tissue layer around a fascicle
Endomysium is the connective tissue around the fibres themselves

Question 2

Sarcoplasmic reticulum

Answer 2

Sarcoplasmic reticulum is an important calcium store for skeletal muscle which is essential for skeletal muscle contraction

Question 3

T tubule

Answer 3

T tubule is important for conducting depolarisation into the inside of the skeletal muscle cell

Question 4

Sarcomere

Answer 4

Sarcomere is the region between Z discs/lines

Question 5

Nerve

Answer 5

Nerve = bundles of icons from motor neurons that reside in the spinal cord which innervate these muscle fibres

Question 6

What else is in skeletal muscle ?

Answer 6

In the skeletal muscle there are also blood vessels and veins and capillaries which are important for supplying nutrients and oxygen to the muscle

Question 7

Sliding filament theory of skeletal muscle contraction summary

Answer 7

Sliding filament theory of skeletal muscle contraction - filaments slide across each other to provide force and skeletal muscle shortening, each of these filaments by themselves do not get shorter by they slide over each other so the overall skeletal muscle gets shorter and therefore the sarcomere gets shorter

Question 8

The skeletal muscle fibre (cell) - Sarcolemma

Answer 8

Skeletal muscle fibre membrane

Question 9

The skeletal muscle fibre (cell) - myofibril

Answer 9

Inside the myofibrils are the myofilaments

Question 10

The skeletal muscle fibre (cell) - myofilaments

Answer 10

actin and myosin

Question 11

The skeletal muscle fibre (cell) - mitochondria

Answer 11

Mitochondria = powerhouses of the cells, provide ATP for energy and it is an essential energy substrate for skeletal muscle contraction when we look at cross bridge cycling

Question 12

The skeletal muscle fibre (cell) - sarcoplasmic reticulum

Answer 12

Sarcoplasmic reticulum = calcium store and has an arrangement such that it is situated right next to a structure called the T tubule or the transverse tubule

Question 13

NMJ synapse forms on the …

Answer 13

The NMJ synapse forms on the outside on the sarcolemma and it causes a depolarisation and action potential which propagates actively along the sarcolemma and this depolarisation needs to get from the membrane to the inside of the muscle cell and it does this via propagation into the T tubules

Question 14

Excitation contraction coupling summary

Answer 14

Action potential in the NMJ causes the release of acetylcholine which binds to nicotinic acetylcholine receptors which depolarises the cell which triggers an action potential and this action potential is due to the active probation due to the opening of voltage dataed sodium channels and this action potential propagates in every direction on the skeletal muscle as well as down the t tubules and this action potential depolarisation is sensed by the voltage sensor which relays this to the calcium channel through the physical coupling and causes the calcium channel to open

Question 15

Excitation contraction coupling - Ballooning of sarcoplasmic reticulum

Answer 15

Ballooning of the sarcoplasmic reticulum as it comes close to/against the T tubule which is called the cisterna (cistern of the sarcoplasmic reticulum)

Question 16

Excitation contraction coupling - voltage gated channels

Answer 16

Voltage gated channels (including Cl- channels) - mainly sodium channels for active propagation, the Cl- channels are important for repolarisation which is going to open and bring the potential back to RMP therefore it ensures that depolarisation does not last for too long

Question 17

Excitation contraction coupling -voltage sensor

Answer 17

Voltage sensor - DHPR senses the change in membrane protenial as an action potential propagates down into the T-tubule and this voltage sensor is physically coupled to a calcium channel on the sarcoplasmic reticulum such that changes in voltage out in the T-tubule can be relayed and cause opening of this calcium channel

Question 18

Excitation contraction coupling - Ca2+ pump

Answer 18

Ca2+ pump - Ca2+ is actively pumped into the sarcoplasmic reticulum to get it out of the cytosol where the actin/myosin are and brings it in to store it away in the sarcoplasmic reticulum store

Question 19

Excitation contraction coupling steps

Answer 19

Actin and myosin are sensitive to calcium
The voltage can be sensed by the voltage sensor and can cause the opening of the calcium channel which allows for calcium to flow out of the sarcoplasmic reticulum and into the cytosol
Voltage sensor aka dihydropyridine receptor (protein in the T tubule membrane that senses the action potential as it comes down)
Ca2+ channel aka ryanodine receptor - sits in the membrane of the sarcoplasmic reticulum, the voltage sensor is physically coupled to this Depolarised voltage sensor causes Ca2+ channel to open and as soon as it opens there is going to be a massive calcium efflux from the inside of the SR into the cytosol
If Ca2+ levels stay too high for too long then we will get continual skeletal muscle contraction therefore continued force development
Ca2+ pump aka SERCA (sarcoplasmic endoplasmic reticulum calcium ATPase) - once contraction is over we need a way to get calcium back in to terminate the skeletal muscle twitch, the calcium is pumped back in by the SERCA pump which uses ATP to pump Ca2+ back into the sarcoplasmic reticulum to terminate skeletal muscle contraction i.e. to terminal cross bridge cycling

Question 20

SERCA

Answer 20

Ca2+ pump aka SERCA (sarcoplasmic endoplasmic reticulum calcium ATPase) - once contraction is over we need a way to get calcium back in to terminate the skeletal muscle twitch, the calcium is pumped back in by the SERCA pump which uses ATP to pump Ca2+ back into the sarcoplasmic reticulum to terminate skeletal muscle contraction i.e. to terminal cross bridge cycling

If Ca2+ levels stay too high for too long then we will get continual skeletal muscle contraction therefore continued force development

Question 21

Ryanodine receptor

Answer 21

Ca2+ channel aka ryanodine receptor - sits in the membrane of the sarcoplasmic reticulum, the voltage sensor is physically coupled to this Depolarised voltage sensor causes Ca2+ channel to open and as soon as it opens there is going to be a massive calcium efflux from the inside of the SR into the cytosol

Question 22

Dihydropyridine

Answer 22

Voltage sensor aka dihydropyridine receptor (protein in the T tubule membrane that senses the action potential as it comes down)

Question 23

Normal heat production in muscles

Answer 23

Heat is a byproduct of muscle activity

Needed to maintain body temperature

Question 24

Hyperthermia and heat production in muscles

Answer 24

Hyperthermia - when body temperature is raised above normal. Can lead to nausea, vomiting, headaches, confusion…and eventually death

Question 25

Generation of heat in muscles explained

Answer 25

SR Ca2+ ATPase = SERCA Ca2+ pump - hydrolyses ATP to ADP + Pi to pump calcium back into the cell and this process generates heat. Lots of Ca2+ in cytosol therefore need lots of ATP therefore generates lots of heat
The production of new ATP also forms heat
Having very active muscles (need more ATP made) and pumping calcium produces heat

Question 26

Malignant hyperthermia

Answer 26

Autosomal dominant, life-threatening disease (can go on for many years without realised that there is an issue)
Due to mutations in ryanodine receptor (RyR) (on SR) or dihydropyridine receptor (DHPR) (on T tubule)
Triggered by volatile anaesthetics (e.g. halothane) - interferes with the receptor that has the mutation and either increases the active of calcium channels or the function of the voltage sensors cause a massive increase in the amount of release Ca2+
Causes muscle rigidity, a hypermetabolic state (therefore more heat because of the ATP used for SERCA) and increased CO2 production
Body temperature can pass 41 degrees very rapidly (therefore can lead to death)

Question 27

ACh amount released during each successive action potential

Answer 27

depletion phenomenon - less ACh is released from the motor neuron during eachh successive action potential

Question 28

The cross bridge cycle - calcium

Answer 28

Caclium is going to interact with actin to allow actin and myosin to interact with each other and have the sliding of filaments over each other to generate muscle tension. The single action potential triggers a switch which is a short period of force generation that lasts for a short amount of time

Calcium comes in and changes the arrangement of the tropomyosin and actin which allows the myosin head to interact with the actin, getting force generation by the flexion of this myosin head and the flexion of the myosin head exerts force on the actin

Question 29

Myosin states

Answer 29

Myosin with a myosin head and this can either be in a flexed state or in an energised state when it has the ATP hydrolysed

Question 30

Tropomyosin is a part of

Answer 30

actin

Question 31

Magnesium is important for

Answer 31

ATP hydrolysis which is part of the cross bridge cycle

Question 32

Thick filament

Answer 32

myosin

Question 33

Thin filament

Answer 33

actin

Question 34

Tropomyosin

Answer 34

Tropomyosin is a long, thin beaded structure that runs along the entire length of the actin and this tropomyosin usually blocks the myosin binding sites, troponin is a part of tropomysosin and has a calcium binding site on it so it is actually the calcium sensor that binds it and then causes a conformational change in tropomyosin to expose these myosin binding sites on the actin

Question 35

Myosin

Answer 35

Myosin has heavy chains and light chains, myosin has 2 heads and they have actin binding sites on the end of the myosin head and they have ATP binding sites. Myosin head wants to bind to actin but it just cannot under resting conditions because tropomyosin is binding these myosin binding sites so in order to get interaction and skeletal muscle contraction and force generation the tropomyosin must be moved

Question 36

Actin and myosin interaction

Answer 36

Actin has sites that myosin can bind
In low Ca2+ concentrations these are covered by tropomyosin
Ca2+ bings to troponin, tropomyosin moves off, myosin heads can engage and then you get cross bridge formation and this is known as the cross bridge cycle

Question 37

Troponin

Answer 37

Ca2+ bings to troponin, tropomyosin moves off, myosin heads can engage and then you get cross bridge formation and this is known as the cross bridge cycle

Troponin is attached to the protein tropomyosin and lies within the groove between actin filaments in muscle tissue. In a relaxed muscle, tropomyosin blocks the attachment site for the myosin crossbridge, thus preventing contraction.

Question 38

The cross bridge cycle steps

Answer 38

When ATP is hydrolysed to ADP+Pi it stays on the myosin head, the myosin head goes from flexed to the extended position which is known as the energised state
ADP+Pi released and this needs to occur in order for the myosin head to be flexed and for force to be generated
No ATP then the head stays attached as all of the myosin heads are unable to detach from the actin
summary of the cross bridge cycle - Calcium binding onto troponin C which interacts with tropomyosin and moves the tropomyosin off these myosin binding sites, we have ATP that comes on and allows the myosin head to detach from the actin and when the ATP is hydrolysed the myosin head can go back to the energised state which means that the head can interact with actin (provided the tropomyosin has been moved off) and the final step is for the ADP and the phosphate to be removed from the myosin head which is when force can be generated